During recent years a new wave of video games, "serious games," has been developed and implemented as a psychotherapeutical complement in various treatments. The objective of our study was to systematically assess the literature on "serious games" and their effectiveness when employed as a complement or psychological support in the treatment of several illnesses. We searched electronic databases and reviewed studies published up until October 2010. The games included in the review were Re-Mission, Personal Investigator, Treasure Hunt, Play Attention and an unnamed video game. Two of the nine articles were descriptive; in the remaining seven studies a favorable outcome was obtained. The reported improvements included: elevated self-esteem, higher self-efficacy, increased knowledge, awareness of the illness, adherence to treatment and problem solving skills, and enhanced outcome on cognitive and behavioral aspects of aggression. In conclusion, well-produced serious games might lead to potential behavioral improvements for patients suffering from a range of medical illnesses.