Past literature reviews of gain-framed versus loss-based health messages have been inconsistent and inconclusive. To resolve this and provide a clearer pattern, this review focuses on the individual or person-specific characteristics of target audiences. The results indicate that by answering the following four questions about a target audience, one can predict whether a gain-framed or a loss-based health message will be more effective. 1) Is there a low (versus high) level of involvement in the issue? 2) Is there a high (versus low) certainty of the outcome? 3) Is there a low (versus high) preference for risk? 4) Is there a heuristic (versus piecemeal) processing style? The profiling of audiences on these factors has two distinct benefits; it resolves many of the seeming inconsistencies in past positive–negative and gain–loss message research (such as fear appeals working better with experts than nonexperts) and it helps predict which type of message will be most effective with a given audience.