Spiro starred in the TBS original comedy series My Boys. She played the role of P.J., a twenty-something “guy's girl”, and sports reporter who tries to find romance within her world that is dominated by male friends. The series wrapped its fourth and final season on TBS in 2010.
Spiro was scheduled to star in the planned 2010–11 television series Love Bites, but fell out of the role in June 2010 due to other contractual obligations. Spiro was also cast alongside Nicolas Cage and Nicole Kidman in the thriller, Trespass. She was a guest star on the Showtime 2011 season of Dexter. For the 2012–13 season, she had the lead role in the Fox-TV medical/crime drama The Mob Doctor.