Lopez was the first Mexican-American to host a late-night talk show on an English-language network in the United States.

During interviews, Lopez said that he would bring the change to late-night television and that he wants the show to reach a diverse audience.

The show debuted on November 9, 2009, with guests Kobe Bryant and Eva Longoria, as well as a special appearance from Ellen DeGeneres and a musical performance from Carlos Santana.

Hours before O'Brien's Legally Prohibited from Being Funny on Television Tour, O'Brien officially announced he had signed with TBS to create his own late-night talk show at 11:00 pm beginning in November 2010, thus pushing Lopez Tonight back to midnight.

Today, not long ago—a couple of hours ago—it was announced that TBS is not renewing George Lopez's show for a third season.

Sketches introduced on the show include Bullet Wound or Not a Bullet Wound, a stereotypical game show similar to Jay Leno's "Jaywalking" where guests must answer seemingly racist questions, Creepy Little White Girl in which a horrific little girl appears on the stage to deliver bad news, The Jersey Shore Presents, a mocking piece where cast members of Jersey Shore star in hit movies, Sweet Tweets where Lopez answers questions submitted from Twitter, WWE Superstars Karaoke where many WWE Superstars performed karaoke songs, Justin Bieber's Memories a segment that mocks Justin Bieber and his childhood, and Eric Estrada where colored lights flash and various guests, including Benjamin Bratt and Jon Cryer come out of the double doors in a California Highway Patrol motorcycle uniform.

The band consisted of leader and keyboard player Michael Bearden, guitarist Tommy Organ, bass player Alex Al, percussionist Lenny Castro, trumpeter Bill Churchville, drummer Robin DiMaggio, and saxophonist Sean Holt.

[5] Matthew Gilbert of The Boston Globe claims "Lopez has a full-throated energy and a weakness for sophomoric guy humor that can be grating, especially since his show will air Monday through Thursday nights.