| No. | Original air date | Guest(s) | Musical/entertainment guest(s) |
| 2628 | September 2, 2008 | Jarod Miller, Jason Lezak | Ra Ra Riot |
| 2629 | September 3, 2008 | Nicolas Cage, Vivica A. Fox | Delta Spirit |
| 2630 | September 4, 2008 | Dr Phil Mcgraw, Kevin Connolly | Adele |
| 2631 | September 5, 2008 | Jerry O'Connell, Tim Gunn | Christian Lander |
| 2632 | September 8, 2008 | Howie Mandel, Nastia Liukin | Bon Iver |
| 2633 | September 9, 2008 | Keira Knightley, Tyler Perry | Bill Burr |
| 2634 | September 10, 2008 | Curtis '50 Cent' Jackson, Kaitlin Olson | Gym Class Heroes |
| 2635 | September 11, 2008 | Serena Williams, Amy Sedaris | Meiko |
| 2636 | September 12, 2008 | Eva Mendes, Luke Russert | The Fab Faux |
| 2637 | September 15, 2008 | Samuel L. Jackson, Ricky Gervais | Marc Broussard |
| 2638 | September 16, 2008 | Martha Stewart, Harland Williams | Kasey Chambers & Shane... |
| 2639 | September 17, 2008 | Ray Liotta, Marc Maron | Loudon Wainwright III |
| 2640 | September 18, 2008 | Anderson Cooper, Willie Nelson | Southside Johnny with La... |
| 2641 | September 19, 2008 | Ice-T, Dwyane Wade | Shane Mauss |
| 2642 | September 22, 2008 | Diane Lane, Patton Oswalt | Little Feat |
| 2643 | September 23, 2008 | Billy Bob Thornton, Aasif Mandvi | Kenny Shopsin |
| 2644 | September 24, 2008 | Jaime Pressly, Little Britain | Lenka |
| 2645 | September 25, 2008 | Julianne Moore, Zachary Levi | Jakob Dylan with Norah... |
| 2646 | September 26, 2008 | Brooke Shields, Robert Reich | Amos Lee |
| 2647 | September 29, 2008 | Bill Maher, Simon Pegg | The Watson Twins |
| 2648 | September 30, 2008 | Julia Louis-Dreyfus, Michael Cera | Nate Bargatze |
| 2649 | October 1, 2008 | Robin Wright Penn, Louis C.K. | Department of Eagles |
| 2650 | October 2, 2008 | Tom Arnold, Flavor Flav | Ben Folds |
| 2651 | October 3, 2008 | Greg Kinnear, J.J. Abrams | Nick Cave - the Bad Seeds |
| 2652 | October 6, 2008 | Felicity Huffman, Jason Sudeikis | Jenny Lewis |
| 2653 | October 7, 2008 | Russell Crowe, Alicia Keys | Death Cab for Cutie |
| 2654 | October 8, 2008 | Molly Shannon, Jason Ritter | Noah McCullough |
| 2655 | October 9, 2008 | Dennis Quaid, Lance Mackey | Sarah McLachlan |
| 2656 | October 10, 2008 | LL Cool J, Oliver Stone | Dead Confederate |
| 2657 | October 13, 2008 | Christian Slater, Brian Posehn | Flobots |
| 2658 | October 14, 2008 | Harry Connick Jr., Richard Lewis | O.A.R. |
| 2659 | October 15, 2008 | Bill Murray, Rob Corddry | Ray LaMontagne |
| 2660 | October 16, 2008 | Josh Brolin, Shaun Ellis - Helen Jeffs | Nikka Costa |
| 2661 | October 17, 2008 | Mike Birbiglia, Edward Norton | Chris 'ludacris' Bridges |
| 2662 | October 27, 2008 | Charles Barkley, Justin Long | Annuals |
| 2663 | October 28, 2008 | Tina Fey, Peter Sarsgaard | The Black Crowes |
| 2664 | October 29, 2008 | Tracy Morgan, Paget Brewster | The Last Shadow Puppets |
| 2665 | October 30, 2008 | Jada Pinkett-Smith, Rachel Maddow | Pink |
| 2666 | October 31, 2008 | Mary-Kate Olsen, Will Forte | Tom Nardone |
| 2667 | November 3, 2008 | Brian Williams, Bill Bellamy | The Decemberists |
| 2668 | November 5, 2008 | Dennis Hopper, Katt Williams | Phil Lesh & Friends |
| 2669 | November 6, 2008 | Elvis Costello, Madeleine Albright | Lordi |
| 2670 | November 7, 2008 | Ricky Gervais, Vera Farmiga | Chromeo |
| 2671 | November 10, 2008 | Andy Richter, Jim Cramer | Tom Papa |
| 2672 | November 11, 2008 | Seth Green, Artie Lange | Conor O'Berst |
| 2673 | November 12, 2008 | Tom Brokaw, Frank Caliendo | Joshua Radin |
| 2674 | November 13, 2008 | Paul Rudd, John Stamos | Boz Scaggs |
| 2675 | November 14, 2008 | Masi Oka, Alan Zweibel | Rock of Ages |
| 2676 | November 17, 2008 | Snoop Dogg, Brian Regan | Blitzen Trapper |
| 2677 | November 18, 2008 | Jeff Corwin, Debra Messing | John Hodgman |
| 2678 | November 19, 2008 | Martin Short, Sarah Vowell | Margot & the Nuclear So and... |
| 2679 | November 20, 2008 | Rosie O'Donnell, Becki Newton | Brian Wilson |
| 2680 | November 21, 2008 | Kiefer Sutherland, Rachel Maddow | Vampire Weekend |
| 2681 | November 24, 2008 | Hugh Jackman, Marge Klindera | Tom Morello & The... |
| 2682 | November 25, 2008 | Kanye West, Seth McFarlane | |
| 2683 | November 26, 2008 | Ethan Hawke, Nikki Reed | Plain White T's |
| 2684 | December 8, 2008 | Stephen Colbert, Keri Russell | The Lee Boys |
| 2685 | December 9, 2008 | Hugh Laurie, Joel McHale | The Gaslight Anthem |
| 2686 | December 10, 2008 | Jennifer Connelly, Bradley Cooper | Alec Greven |
| 2687 | December 11, 2008 | Bill Hader, Jessica Szohr | Tony Bennett |
| 2688 | December 12, 2008 | Don Rickles, John Leguizamo | Erran Baron Cohen |
| 2689 | December 15, 2008 | Amy Adams, Eddie Izzard | John Legend |
| 2690 | December 16, 2008 | Eva Mendes, Ken Mink | Fleet Foxes |
| 2691 | December 17, 2008 | Jeff Goldblum, David Gregory | Charlie Viracola |
| 2692 | December 18, 2008 | Matthew Broderick, Paul F. Tompkins | Little Big Town |
| 2693 | December 19, 2008 | Jennifer Aniston, Judah Friedlander | Pilobolus |
| 2694 | December 22, 2008 | Carson Daly, Steve Schirripa | Bela Fleck & The Flecktones |
| 2695 | December 23, 2008 | Dustin Hoffman, Greg Giraldo | Old Crow Medicine Show |
| 2696 | January 5, 2009 | Benicio Del Toro, Sarah Chalke | Doyle & Debbie |
| 2697 | January 6, 2009 | Kate Hudson, Tim Daly | Bang Camaro |
| 2698 | January 7, 2009 | Chris Meloni, Sheriff Joe Arpaio | The Derek Trucks Band |
| 2699 | January 8, 2009 | Howie Mandel, Anthony Mackie | Lady Antebellum |
| 2700 | January 12, 2009 | Daniel Radcliffe, Dr. Drew Pinsky | Eric Hutchinson |
| 2701 | January 13, 2009 | Rosario Dawson, Donald Faison | Susan Tedeschi |
| 2702 | January 14, 2009 | Salma Hayek, Paul Bettany | Patty Loveless |
| 2703 | January 15, 2009 | Bob Costas, Fred Armisen | Robert Schimmel |
| 2704 | January 19, 2009 | Teri Hatcher, Aries Spears | Q-Tip |
| 2705 | January 20, 2009 | William H. Macy, Steve Nash | Los Straitjackets |
| 2706 | January 21, 2009 | Meredith Vieira, Marc Maron | Fall Out Boy |
| 2707 | January 22, 2009 | Ron Howard, Eric McCormack | John Cassidy |
| 2708 | January 26, 2009 | John C. Reilly, Jimmie Johnson | The Walkmen |
| 2709 | January 27, 2009 | Matt Lauer, Steve Harvey | M83 |
| 2710 | January 28, 2009 | Evangeline Lilly, Kevin Connolly | Cold War Kids |
| 2711 | January 29, 2009 | Jon Stewart, Mary Lynn Rajskub | Mike Birbiglia |
| 2712 | February 2, 2009 | Kathy Griffin, Paula Deen | Amy LaVere |
| 2713 | February 3, 2009 | Seth Meyers, Johnny Knoxville | Zac Brown Band |
| 2714 | February 4, 2009 | Jon Hamm, Ginnifer Goodwin | Theresa Andersson |
| 2715 | February 5, 2009 | Brian Williams, Taraji P. Henson | Nate Bargatze |
| 2716 | February 9, 2009 | Clive Owen, Judah Friedlander | Brett Dennen, Matisyahu |
| 2717 | February 10, 2009 | Norm Macdonald, Gordon Ramsay | Levon Helm |
| 2718 | February 11, 2009 | Jimmy Fallon, Rose Byrne | John Pizzarelli |
| 2719 | February 12, 2009 | Alec Baldwin, Eliza Dushku | They Might Be Giants |
| 2720 | February 13, 2009 | Isla Fisher, Jonas Brothers | Dan Auerbach |
| 2721 | February 16, 2009 | Bob Saget | The Newno2 |
| 2722 | February 17, 2009 | Jason Sudeikis | |
| 2723 | February 18, 2009 | Nathan Lane | |
| 2724 | February 19, 2009 | Jerry Seinfeld | Craig Bierko |
| 2725 | February 20, 2009 | Andy Richter | The White Stripes |