Video games are a source of entertainment for a wide population and have varied effects on well-being. The purpose of this article is to comprehensively examine game-play research to identify the factors that contribute to these disparate well-being outcomes and to highlight the potential positive effects. On the basis of existing literature, we argue that the effects of gaming on well-being are moderated by other variables, such as motivations for gaming and video-game characteristics. Specifically, the inclusion of social activity can benefit prosocial behaviors and affect the relationship between violent video games and aggression that some studies have demonstrated. Moreover, the research on the relationship between violent video games and aggression depends greatly on individual and sociocontextual variables outside of game play. The inclusion of physical activity in games can provide an improvement in physical health with high levels of enjoyment, potentially increasing adherence rates. Overall, following our review, we determined that the effects of gaming on well-being are moderated by and depend on the motivation for gaming, outside variables, the presence of violence, social interaction, and physical activity. Thus, we argue that there is potential for an “optimal gaming profile” that can be used in the future for both academic- and industry-related research.