On October 1, 2005, she announced at Wizard World Boston that shooting had begun for Nobel Son in which she would star with Alan Rickman, Danny DeVito, Bill Pullman, and Peter Boyle. The movie was released at the 2007 Tribeca Film Festival and received exceptional reviews. Another project is On Broadway, an independent movie filmed in her native Boston. The movie is receiving great reviews and a few of them highlight Dushku's performance. It is currently being shown in many independent film festivals and has already won six awards.

Variety announced on August 2, 2006 that Dushku would co-star with Macaulay Culkin in Sex and Breakfast, a dark comedy written and directed by Miles Brandman. The movie was released in Los Angeles in November 30, 2007 and on DVD in January 22, 2008. She starred in Open Graves, a 2008 horror-thriller about a satanic game co-starring Mike Vogel. She will play the main character in The Thacker Case and The Alphabet Killer, both based on real-life events and upcoming thrillers, one of them directed by Rob Schmidt with whom she had previously worked on Wrong Turn. Both movies will be released in 2008. The Alphabet Killer contains Dushku's first topless scene. She also appeared, along with Alan Rickman, Bill Pullman, Chris Pine and Rachel Taylor, in Bottle Shock, a drama about Napa valley wine. The film was directed by Randall Miller, who helmed Nobel Son.

On August 26, 2007, Dushku signed a development deal with Fox Broadcasting and 20th Century Fox. Under the pact, the network and the studio will develop projects tailor-made for the actress. They also will approach her with existing pitches and scripts. Consequently, it was announced on October 31 that Dushku had lured Joss Whedon, famous for creating the Buffy The Vampire Slayer and Firefly series, back to TV, as they agreed to create a new show called Dollhouse. Dushku will play the main character 'Echo' and serve as a producer on the show, which will air on Fox during the 2008-09 TV Season.

• Noah's Ark: The New Beginning (2008) (post-production) (voice) .... Zalbeth
• Open Graves (2009) (completed) .... Erica
  
• "Dollhouse" .... Echo (7 episodes, 2009)
       - Echoes (2009) TV episode .... Echo
       - Man on the Street (2009) TV episode .... Echo
       - True Believer (2009) TV episode .... Echo
       - Gray Hour (2009) TV episode .... Echo
       - Stage Fright (2009) TV episode .... Echo
        (2 more)
• The Thacker Case (2008) .... Monica Wright
• Saints Row 2 (2008) (VG) .... Shaundi
• The Alphabet Killer (2008) .... Megan Paige
• Bottle Shock (2008) .... Joe
• Sex and Breakfast (2007) .... Renee
  ... aka Sex & Breakfast (Australia)
• "Ugly Betty" .... Cameron Ashlock (1 episode, 2007)
       - Giving up the Ghost (2007) TV episode .... Cameron Ashlock
• Nobel Son (2007) .... City Hall
• On Broadway (2007) .... Lena Wilson
• Nurses (2007) (TV) .... Eve Morrow
  ... aka Philidelphia General (USA: informal title)
• The Last Supper (2006) .... Waitress
• Ryû ga gotoku (2005) (VG) (voice: English version) .... Yumi
  ... aka Yakuza (USA)
• "Tru Calling" .... Tru Davies (27 episodes, 2003-2005)
       - 'Twas the Night Before Christmas... Again (2005) TV episode .... Tru Davies
       - Enough (2005) TV episode .... Tru Davies
       - The Last Good Day (2005) TV episode .... Tru Davies
       - In the Dark (2005) TV episode .... Tru Davies
       - Grace (2005) TV episode .... Tru Davies
        (22 more)
• "That '70s Show" .... Sarah (1 episode, 2005)
       - It's All Over Now (2005) TV episode .... Sarah
• The Kiss (2003) (V) .... Megan
• Buffy the Vampire Slayer: Chaos Bleeds (2003) (VG) (voice) .... Faith Lehane
• "Buffy the Vampire Slayer" .... Faith / ... (20 episodes, 1998-2003)