She had roles in a few movies, including Very Mean Men (2000), Spiders (2000), Frozen Stars (2003) and Replicant. She was first noticed in the mainstream when she joined the cast of Spin City in 2000, playing Angie Ordonez for one season.
After this, she joined Donnie Wahlberg and Neal McDonough in the 2002 series Boomtown, in which she played Teresa, a paramedic, a role for which she received the "Imagen Award for Best Supporting Actress". Initially a success, Boomtown began to struggle, and Lana's character became a police academy rookie, so as to tie her more closely to the rest of the show. That program was cancelled just two episodes into its second season.
Parrilla guest starred in shows such as JAG, NYPD Blue and Six Feet Under. In 2005, Parrilla took a recurring guest role on the fourth season of 24 as Sarah Gavin, a Counter Terrorist Unit agent. After just six episodes, Lana was promoted to a main cast member, but in the 13th episode, she was written out for reasons unknown, after her character demanded a promotion from temporary head Michelle Dessler, which was denied.
In 2006, Parrilla starred in the NBC summer series Windfall, alongside Luke Perry, fellow former 24 castmember Sarah Wynter, and Parilla's former Boomtown castmate Jason Gedrick. In 2007, Parrilla guest-starred as a character called Greta in the last three episodes of the third season of ABC's Lost.
In 2008, she starred in the Lifetime movie The Double Life of Eleanor Kendall, in which she played Nellie, a divorcee whose identity had been stolen. In June 2008, she starrred in the CBS summer series Swingtown as Trina Decker, a woman who is part of a swinging couple.
In 2010, Parrilla starred in the Jerry Bruckheimer-produced Miami Medical on CBS, which had a short run towards the end of the 2009-10 television season before being cancelled in July 2010. From 2010 to 2011, she made many guest appearances of TV shows, such as Covert Affairs, Medium, The Defenders and Chase.