Panabaker followed her initial appearances in commercials with roles in television, including a part in The Guardian (for which she won a Young Artist Award), as well as other television series including Malcolm in the Middle, Law & Order: Special Victims Unit, Medium, and Summerland, and the Disney Channel Original Movie Stuck in the Suburbs.
She also appeared in the Lifetime Television productions Sex and the Single Mom and Mom at Sixteen, as well as the well-reviewed miniseries Empire Falls.
She considers Empire Falls to be her big break, as it gave her the confidence to pursue her career.
In addition, Panabaker appeared in stage productions with roles in musical theater, including West Side Story, Pippin, Once upon a Time, and Beauty Lou and the Country Beast.
In 2004, she starred in the ABC film "Searching for David's Heart".
In 2005, Panabaker co-starred in two widely released theatrical films, Sky High and Yours, Mine and Ours.
Her next role was in the film Home of the Giants (2008).
She also had a supporting role in the film Mr. Brooks.
In the Disney Channel original movie Read It and Weep, she plays Is, an alternate version of Jamie, who was played by her real-life sister, Kay Panabaker.

From 2006 to 2008, Panabaker starred in the CBS television drama Shark, playing Julie Stark, the daughter of the lead character.
In 2009, Panabaker played Jenna, a main character in the Friday the 13th remake.
Panabaker next starred in the films The Crazies and The Ward.

In 2011, Panabaker starred as Katie Lapp, the lead character in the Hallmark Channel movie The Shunning, based on the novel by Beverly Lewis.
She was to reprise her role in the 2013 sequel The Confession, but a scheduling conflict forced her to drop out, and the role was recast.
In 2013, she starred in another Hallmark Channel movie, Nearlyweds.
On May 5, 2013, Panabaker joined actors including Philip Baker Hall, Bill Pullman, and Maggie Siff in performing at Cedering Fox's WordTheatre, where they read aloud contemporary short fiction.
In 2014, Panabaker starred in Bradley D. King's award-winning science-fiction film Time Lapse, for which she won the award for Best Actor/Actress at the 2014 London Independent Film Festival.

In April 2014, she guest starred as Caitlin Snow in a second-season episode of the CW series Arrow; since October 2014, she has starred as the same character in the spinoff series The Flash.
Panabaker made her directorial debut with the eighteenth episode of the series' fifth season, entitled "Godspeed".
Panabaker followed her initial appearances in commercials with roles in television, including a part in The Guardian (for which she won a Young Artist Award), as well as other television series including Malcolm in the Middle, Law & Order: Special Victims Unit, Medium, and Summerland, and the Disney Channel Original Movie Stuck in the Suburbs. She also appeared in the Lifetime Television productions Sex and the Single Mom and Mom at Sixteen, as well as the well-reviewed miniseries Empire Falls. She considers Empire Falls to be her big break, as it gave her the confidence to pursue her career. In addition, Panabaker appeared in stage productions with roles in musical theater, including West Side Story, Pippin, Once upon a Time, and Beauty Lou and the Country Beast. In 2004, she starred in the ABC film "Searching for David's Heart". In 2005, Panabaker co-starred in two widely released theatrical films, Sky High and Yours, Mine and Ours. Her next role was in the film Home of the Giants (2008). She also had a supporting role in the film Mr. Brooks. In the Disney Channel original movie Read It and Weep, she plays Is, an alternate version of Jamie, who was played by her real-life sister, Kay Panabaker.
From 2006 to 2008, Panabaker starred in the CBS television drama Shark, playing Julie Stark, the daughter of the lead character. In 2009, Panabaker played Jenna, a main character in the Friday the 13th remake. Panabaker next starred in the films The Crazies and The Ward.
In 2011, Panabaker starred as Katie Lapp, the lead character in the Hallmark Channel movie The Shunning, based on the novel by Beverly Lewis. She was to reprise her role in the 2013 sequel The Confession, but a scheduling conflict forced her to drop out, and the role was recast. In 2013, she starred in another Hallmark Channel movie, Nearlyweds. On May 5, 2013, Panabaker joined actors including Philip Baker Hall, Bill Pullman, and Maggie Siff in performing at Cedering Fox's WordTheatre, where they read aloud contemporary short fiction. In 2014, Panabaker starred in Bradley D. King's award-winning science-fiction film Time Lapse, for which she won the award for Best Actor/Actress at the 2014 London Independent Film Festival. 
In April 2014, she guest starred as Caitlin Snow in a second-season episode of the CW series Arrow; since October 2014, she has starred as the same character in the spinoff series The Flash. Panabaker made her directorial debut with the eighteenth episode of the series' fifth season, entitled "Godspeed".
Danielle Panabaker