Obesity and other inactivity related diseases are increasing at an alarming rate especially in Western societies. Because of this, it is important to understand the regulating mechanisms involved in physical activity behavior. Much research has been done in regard to the psychological determinants of physical activity behavior; however, little is known about the underlying genetic and biological factors that may contribute to regulation of this complex trait. It is true that a significant portion of any trait is regulated by genetic and biological factors. In the case of voluntary physical activity behavior, these regulating mechanisms appear to be concentrated in the central nervous system. In particular, the dopamine system has been shown to regulate motor movement, as well as motivation and reward behavior. The pattern of regulation of voluntary physical activity by the dopamine system is yet to be fully elucidated. This review will summarize what is known about the dopamine system and regulation of physical activity, and will present a hypothesis of how this signaling pathway is mechanistically involved in regulating voluntary physical activity behavior. Future research in this area will aid in developing personalized strategies to prevent inactivity related diseases.