Gamification refers to using game attributes in a non-gaming context. Health professions educators increasingly turn to gamification to optimize students' learning outcomes. However, little is known about the concept of gamification and its possible working mechanisms. This review focused on empirical evidence for the effectiveness of gamification approaches and theoretical rationales for applying the chosen game attributes. We systematically searched multiple databases, and included all empirical studies evaluating the use of game attributes in health professions education. Of 5044 articles initially identified, 44 met the inclusion criteria. Negative outcomes for using gamification were not reported. Almost all studies included assessment attributes (n = 40), mostly in combination with conflict/challenge attributes (n = 27). Eight studies revealed that this specific combination had increased the use of the learning material, sometimes leading to improved learning outcomes. A relatively small number of studies was performed to explain mechanisms underlying the use of game attributes (n = 7). Our findings suggest that it is possible to improve learning outcomes in health professions education by using gamification, especially when employing game attributes that improve learning behaviours and attitudes towards learning. However, most studies lacked well-defined control groups and did not apply and/or report theory to understand underlying processes. Future research should clarify mechanisms underlying gamified educational interventions and explore theories that could explain the effects of these interventions on learning outcomes, using well-defined control groups, in a longitudinal way. In doing so, we can build on existing theories and gain a practical and comprehensive understanding of how to select the right game elements for the right educational context and the right type of student.