The usefulness and effectiveness of specific serious games in the medical domain is often unclear. This is caused by a lack of supporting evidence on validity of individual games, as well as a lack of publicly available information. Moreover, insufficient understanding of design principles among the individuals and institutions that develop or apply a medical serious game compromises their use. This article provides the first consensus-based framework for the assessment of specific medical serious games. The framework provides 62 items in 5 main themes, aimed at assessing a serious game's rationale, functionality, validity, and data safety. This will allow caregivers and educators to make balanced choices when applying a serious game for healthcare purposes. Furthermore, the framework provides game manufacturers with standards for the development of new, valid serious games. (JMIR Serious Games 2014;2(2):e11) doi:10.2196/games.3825