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Guided by prospect theory, a large body of research has investigated the relative effectiveness of gain- and loss-framed message appeals in various health communication contexts. Several meta-analytic reviews (e.g., O'Keefe & Jensen, 2007, 2009), however, suggest that the anticipated relative advantage of each type of frame under certain conditions (e.g., prevention versus detection behavior) was not found in the existing literature. In an effort to explore why such a robust theory in economics and behavioral psychology fails to receive consistent empirical support in health communication research, this theoretical article critically reviews how prospect theory has been applied in research on gain- and loss-framed message effects, with reference to the original prospect theory. Four mismatches were identified upon a closer examination: They differed in terms of conceptualization of riskiness, subjectivity of perceived risk, absence/ presence of required efforts in adopting a behavioral option, and argument framing. The identified four mismatches inspire the integration of prospect theory and major constructs in health behavior theories including response efficacy and perceived susceptibility, thereby offering more nuanced understanding of the use of prospect theory in communicating health.