Objective: Health messages can be framed in terms of the benefits of adopting a recommendation (gain frame) or the costs of not adopting a recommendation (loss frame). In recent years, research has demonstrated that the relative persuasiveness of gain and loss frames can depend on a variety of dispositional factors. This article synthesizes this growing literature to develop our understanding of the moderators of framing. Method: A systematic review of published literature on gain and loss framing was conducted. Articles were retrieved that tested the interaction between framing and moderators representing individual differences in how people are predisposed to think, feel, and behave. The significance and direction of framing main effects and interactions were noted and effect size data extracted where available. Results: Forty-seven reports published between January 1990 and January 2012 were retrieved that reported on 50 unique experiments testing 23 different moderators. Significant interactions with typically small to medium simple main effect sizes were found in 37 of the 50 studies. Consistent interactions were found for factors such as ambivalence, approach–avoidance motivation, regulatory focus, need for cognition, and self-efficacy beliefs. Less consistent effects were found for perceived riskiness of activity, issue involvement, and perceived susceptibility/severity. Conclusion: The relative effectiveness of gain- or loss-framed messages can depend on the disposition of the message recipient. Tailoring the frame to the individual therefore has the potential to maximize message persuasiveness.