Brendon's role as Xander Harris was initially that of the occasional comic relief and plucky sidekick to the lead female character, but in later seasons fewer comedic lines were given to the part. When the series ended in 2003, Brendon joined the cast of a new Fox sitcom, Kitchen Confidential, based on the book by chef Anthony Bourdain. Thirteen episodes were made, but the series was cancelled on December 9 of the same year, after the fourth episode aired with low ratings.
In 2006, he voiced Huntsboy #89 for season 2 of the animated series American Dragon: Jake Long. The series ended on September 1, 2007. His character's final appearance was in the episode "Shaggy Frog", which aired on April 28, 2007.
From July 26 through August 30, 2006, Brendon co-starred with Noah Wyle in the play Lobster Alice, in Los Angeles.
That same year, Brendon reunited with his former Buffy on-screen sweetheart, Charisma Carpenter, in the ABC Family TV movie Relative Chaos.
At a pop culture expo in Sydney, October 2007, he mentioned that he would be joining the cast of the CBS crime drama Criminal Minds as Penelope Garcia's love interest. Since that time he has been in several episodes playing FBI technical analyst Kevin Lynch and it seems as if he will be making random appearances in upcoming episodes.
He is currently playing the lead in David Sedaris’ play The Santaland Diaries. The play runs from November 20-December 20, 2009 at the The Blank Theatre's 2nd Stage in Hollywood,CA.