Tripplehorn has yet to debut as Alex Blake, but since she pulls double duty as a linguistic professor, we expect her to be an ambitious and tough new presence in the BAU. Lest we forget, Brewster was also a replacement, joining the procedural in Season 2 after original cast member Lola Glaudini left. But Brewster's dry, oft-mysterious Emily Prentiss became a fan favorite and had many yearning for a Hotch-Prentiss hookup. (Don't worry, Alex will have a longtime boyfriend.)

It's no easy task to fill a tiger blood-fueled warlock's shoes, but Kutcher's bumbling Walden Schmidt did his best. Extra points for doing away with the shaggy facial hair and not sleeping around (as much) as Charlie Harper did. But you know what would help exorcise the Ghost of Sheen Past? If the show doesn't constantly keep concocting plots about the late bachelor.

CSI was always anchored by Gil Grissom, so it's no doubt that the aging CBS procedural had trouble replacing him when William Petersen decided to leave the show in the middle of Season 9. Though Fishburne was a high-profile replacement, his Dr. Ray Langston never quite clicked with viewers, even though his rivalry with serial killer Nate Haskell took up lots of screen time. When Fishburne didn't renew his contract after Season 11, the producers reinvigorated the show with Danson's D.B. Russell a quirky iconoclast whose by-the-book style brought focus to the team while also keeping things light.

Producers didn't have to brainstorm that hard to write Patinkin's exit. After the actor failed to attend the Season 3 premiere table read, he negotiated out of his contract and his character, Jason Gideon, doesn't show up to work in the second episode, burnt out by the job. Mantegna's David Rossi joined a few episodes later and proved to be a stark contrast to Gideon. Though he lacks Gideon's leadership, Rossi's relaxed approach has been a welcome change to Gideon's intense and overdramatic antics.

McIntyre had the unenviable task of replacing Whitfield in the title role after the former dropped out when his non-Hodgkin's lymphoma returned. Whitfield gave Starz his blessing to continue the show without him, and while McIntyre doesn't carry the same gravitas as Whitfield did, he's doing a respectable job of filling in some very big sandals. Whitfield died in September 2011, four months before Season 2 of Spartacus premiered.

Daphne Maxwell Reid and Janet Hubert-Whitten, The Fresh Prince of Bel-Air Reid and Hubert-Whitten might as well have played two different characters. The latter's original Aunt Viv was feisty and stern with a take-no-prisoners 'tude, but Viv turned into a softer, more genial character when Reid joined the show in Season 4 after Hubert-Whitten was fired. And don't think she's over it yet. Hubert-Whitten had a notorious falling-out with Will Smith and NBC, who she claimed fired her when she refused to agree to episode count and salary reductions.

Tiffani-Amber Thiessen and Shannen Doherty, Beverly Hills 90210 After feuding with her castmates (ahem, Jennie Garth), Doherty left the famous zip code after the fourth season and was replaced by Thiessen's Valerie Malone, a Buffalo bad girl who was the polar opposite from Doherty's Minnesota good girl Brenda Walsh and Thiessen's most famous role, Saved By the Bell's effervescent Kelly Kapowski. Valerie kept things juicy for four years and unlike Brenda, she came back — reformed and happy — in the series finale.

For the second time in her career, Doherty left a TV series (because of a feud with co-star Alyssa Milano, if you believe reports) and it again lasted longer without her than it did with her. Charmed continued for five more seasons following Doherty's exit and McGowan's fierce and fun Paige Matthews jelled better with her bewitching sisters than Doherty's Prue ever did.

One of the few actors who's been both a replacement and a replacee, Sheen joined the sitcom in Season 5 when Fox left after his Parkinson's disease symptoms worsened. The show lasted two more seasons and won Sheen a Golden Globe, but his womanizing (what else is new?) Charlie Crawford was not an adequate substitute for the all-American charm of Fox's Mike Flaherty.

Viewers were stunned when original cast member Kanakaredes chose not to renew her contract just a few weeks before production on Season 7 was set to begin. (The producers wrote her character, Stella Bonasera, out of the show, noting that she'd taken a job running a crime lab in New Orleans.) The show replaced Stella's hard-charging attitude with Ward's Jo Danville, who took a softer, more psychological approach to her work. As a result, the team at the crime lab seems to function more as a family.

Robert Buckley, Shantel VanSanten and Chad Michael Murray, Hilarie Burton, One Tree Hill Buckley (Clay) and Van Santen (Quinn) were introduced in Season 7 after Murray (Lucas) and Burton (Peyton) rode off into the sunset in the Season 6 finale with their baby daughter. But despite the show's best attempts to make the Clay-Quinn love story compelling (Clay has a secret son and a sleep disorder!), Lucas and Peyton remain Tree Hill's ultimate couple.

Sam and Diane came to an end when Long left the sitcom after five seasons to focus on her movie career. Alley's neurotic and awkward Rebecca Howe never captured (or tortured) Sam's heart like Diane did, but their relationship thrived on the same sexual tension without the pretentious snobbishness that Diane had. The show lasted longer with Alley (six years) than with Long.

ER replaced one hunk with a European one after Clooney's Dr. Doug Ross left midway through season 5. Both Dr. Ross and Dr. Luka Kovac had dark pasts, but Ross' fun-loving (and sometimes drunken) ways provided more levity than the brooding Kovac did. Besides, Ross is one-half of ER's royal couple of Doug and Carol (Julianna Margulies). At least Kovac ended up with Margulies' replacement, Maura Tierney's Abby Lockhart.

Despite the breakout success of the show, Fawcett chose not to return to the series after one season, leaving big shoes (and even bigger hair) to fill. Enter Cheryl Ladd as Kris Munroe, the younger sister of Fawcett's Jill. Though Fawcett made intermittent guest appearances, Ladd's youthful energy worked for audiences and she remained on the show until its cancellation.

John Kelly, we hardly knew ya. Caruso infamously left NYPD Blue after the first season to pursue a film career that never flourished. But that allowed Smits to join as Bobby Simone and create one of the best cop duos with Dennis Franz's Andy Sipowicz. His soulful performance anchored the drama for four and a half years, and Bobby's death from a heart ailment is still one of TV's most emotional deaths.

Priscilla Barnes and Jenilee Harrison and Suzanne Somers, Three's Company Suzanne Somers was Three's Company break-out star … until she asked for more money and found herself (almost) entirely out of a job in Season 5. We say almost because — in one of the most awkward transitions in TV history — Somers continued to film semi-regular scenes for the comedy's fifth season featuring her character, Chrissy, phoning home and see how her ex-roommates were doing. As unlucky in love nurse Terri Alden, Barnes was slightly more well-received than Harrison, who played Chrissy's cousin, but neither were ever really able to fill Somers' shoes.

When a TV show is named after you, you're practically irreplaceable, right? Wrong! Harper learned this the hard way when NBC fired her from Valerie for not showing up to work during a much-publicized salary dispute. Her character was killed in a car accident and the comedically gifted Sandy Duncan joined the show as Valerie's on-screen sister-in-law who returned home to help her brother and his three children deal with their grief. The move gave new emotional depth to the previously ho-hum comedy and gave it enough steam to last four more seasons as The Hogan Family.

Perhaps the most famous TV replacement, Bewitched traded one Dick for another when York bowed out after five seasons because of a back injury he suffered while filming They Came to Cordura. Unfortunately, York's sparkling chemistry with Elizabeth Montgomery couldn't be duplicated with the too-stiff, all-too-serious Sargent. Ratings plummeted and the show was canceled after the eighth season.

You won't find a more complicated switcheroo than this one. Goranson left the series at the beginning of the fifth season to attend Vassar, but made sporadic appearances as Becky. Producers eventually decided to recast her with Chalke, a move that didn't go over well with fans because she lacked Goranson's blue-collar, Midwestern appeal. Even worse? Goranson later came back, and she and Chalke alternated the role before Chalke took it over completely in the final ninth season. The show often made inside jokes about the swap. "I can have you replaced, you know," Roseanne told Becky No. 2 once.