Robert De Niro will be Jimmy Fallon's first guest—an unusually intimidating choice to ease first-night jitters, no matter how well their "Are you a pothead Fallon? Could you milk me?"-patter goes in rehearsal.

The rest of the week has some more dependably upbeat bets, including Fallon's former Weekend Update co-anchor Tina Fey and Fever Pitch co-star and producer-in-law, Drew Barrymore. Barrymore is something of a Late Night early-guest good luck charm, having appeared on Conan's very first episode, and that got us thinking about some other legendary First Guests.

Bill Murray on Late Night with David Letterman, 1982. Perhaps the greatest First Guest of all time, Murray kicked off both of Dave Letterman's longtime late night ventures. On the very first Late Night, accompanied by a musical ode to his SNL lounge singer, a mostly incoherent and playfully argumentative Murray suggests the host looks "sedated," before the two segue into a gripping conversation about playing with lint, a longer diatribe about Dave selling out (we think?), and ending on a pledge to make Letterman's life a living hell. Score: 2 1/2 Joaquins out of a possible five, and lots of fun!

Billy Crystal on The Tonight Show with Jay Leno, 1992. An unbelievably prescient Crystal opens with, "I saw Ed McMahon on the corner with a sign that says, 'Will announce for food.'"

Bill Murray on Late Show with David Letterman, 1993. Letterman then invited Murray back to kick off things at his new home on CBS. Murray's shtick is a lot more thought out this time around—he arrives jogging and breathless, explaining "I went to the other place." We then cut to some video of Murray in a hardhat among the crew of construction guys who refurbished the Ed Sullivan Theater. His big finish, which isn't in the video, involved spraypainting Dave's name on his brand new desk. Somehow, it came off as funny, not just pointless and mean-spirited, like the Kevin Spacey Jamba Juice-dumping fiasco.

Goldie Hawn on The Chevy Chase Show, 1993. Widely considered to be one of the most disastrous late show guest appearances—much less First Guest appearances—of all time was when Goldie Hawn kicked things off on The Chevy Chase Show. In rolled-up Daisy Dukes, she talks for what like seems an eternity on the magic of child-rearing, then presents her son with a birthday cake and everyone sings "Happy Birthday to You." Chevy drops the cake, they dance to "La Bamba," a stage manager brings out the real birthday cake, the show cuts to commercial, and you watch in horrified amazement.

Will Ferrell on The Megan Mullally Show, 2006. Want to know how we know Will Ferrell is a good guy? He'll agree to be the first guest on your new talk show, even though it's on in the afternoon, and you're Megan Mullally. You want to know how we know he's a great guy? He does it in American Apparel briefs, and brings a dozen long-stemmed roses. And a taped X keeping his mic on his chest. Couldn't save the show, but it's the thought that counts.