Lopez Tonight celebrates its 100th episode, with guests Kobe Bryant and Louis C.K. with special appearances from Arsenio Hall, Clint Eastwood, Tom Cruise, Donald Trump, Russell Brand, and Eddie Van Halen. At the end of the show, George alongside his band performed the Van Halen song "Panama".
| Name | Type | Role | |
|---|---|---|---|
| Louis C.K. | Guest Star |