The movie hunk has been on board as CSI supervisor Gil Grissom from the start, appearing in all but one episode of the series. His quirky, likable character has been the reason many fans say they've stuck with the show through the nine seasons, turning it into a mega-hit for CBS.
In a recent AOL poll with more than 600,000 respondents, 37 percent said they would not watch CSI once Petersen was gone, and 41 percent said they would decide after seeing how much they liked his replacement, Lawrence Fishburne.
But will viewers really wash their hands of the top-rated series after Petersen bows out in January? History seems to say no. A good show is a good show, although it may take a little time to cozy up to Fishburne.
Here's a peek at a few shows that lost their main characters:
9. Bonanza: Back in the day, this was a powerhouse Western centered around a rich rancher and his three sons, played by Dan Blocker, Michael Landon and Pernell Roberts. Roberts decided he'd grown too big for the small screen and rode into the sunset. His departure never registered so much as a tap on the ratings chart.
8. M*A*S*H: The two leads of the show were Alan Alda as Hawkeye and Wayne Rogers as Trapper John. When Alda emerged as the bigger star, an unhappy Rogers left the show -- and he was replaced by new character B.J., played by Mike Farrell. Ironically, the character of Trapper John came back in a new series starring Pernell Roberts.
7. Cheers: Shelly Long wanted to pursue her movie career, so she left Cheers. The show was able to prosper for another six years without her.
6. Law & Order: Jerry Orbach was the much beloved Det. Lennie Brisco, and when he left the show in 2004 many thought viewers would flee as well. Didn't happen. Orbach died later that year.
5. Roseanne: OK, she wasn't technically the star of the show, but when Lecy Goranson left for college, she was replaced by Sarah Chalke without so much as a plastic surgery story explaination. The Scrubs star now claims title as Second Becky. In one of the strangest casting choices ever, Chalke would simply fill in when Goranson wasn't available, so the two shared the role for a couple of seasons -- but it didn't make much of a ripple in the ratings.
4. Charmed and Beverly Hills 90210: Shannen Doherty just can't play nice with others. She was dropped as Brenda on 90210 and as witch sister Pru on Charmed, once again proving that her departure from a TV series carries a single impact.
3. NYPD Blue: David Caruso decided that his star burned too brightly for a mere hit TV show, so he tossed his role and moved on to nothing much. The series sailed on quite nicely without him. And when he got the CSI: Miami gig, a much humbled Caruso swore he'd never make the mistake of leaving a hit show again.
2. The X-Files: Duchovny's departure from the show, followed closely by Gillian Anderson's Agent Scully farewell, sealed the fate for this series. It never recovered, but tangled mythology and sour storylines didn't help feed viewer interest.
1. ER: Has there ever been a show with a more active revolving door? Anthony Edwards and George Clooney leaving the series should have sounded the death knell, but the show continued to be a strong ratings success until finally winding down to a natural death cycle this season.