The causes of psychopathy, a condition characterized by interpersonal (e.g., superficial charm), affective (e.g., lack of empathy), and behavioral (e.g., impulsive actions) features, remain contested. The present review examines 1 of the most influential etiological models of psychopathy, the response modulation hypothesis (RMH), which proposes that psychopathic individuals exhibit difficulties in adjusting their behavior in the presence of a dominant response set. We conduct a meta-analysis and narrative literature review to examine the RMH quantitatively and qualitatively, estimate the statistical effects of response modulation (RM) deficits in psychopathic individuals, and ascertain the boundary conditions of the RMH. Ninety-four samples from published and unpublished studies involving 7,340 participants were identified for inclusion. Overall results provided some support for the RMH, revealing a small to medium relationship between psychopathy and RM deficits (r = .20, p < .001, d = .41) that extended to both psychopathy dimensions. Moreover, as predicted by the RMH, RM deficits were observed for both affectively neutral and affectively laden tasks. A number of moderators, such as anxiety, laboratory task, dependent measure, psychopathy measure, and race, contributed to significant variability in effect sizes; we also found evidence for potential publication bias using 2 methods, raising questions concerning the robustness of RM findings. An ancillary narrative review revealed that the RMH is inconsistent with a number of replicated findings in the psychopathy literature, suggesting that the RMH, at least in its present form, is unlikely to provide a comprehensive etiological account of psychopathy. Nevertheless, more recent attentional versions of the RMH may hold promise with respect to intervention. Further fruitful directions for research on the RMH, including the use of multiple dependent measures of RM and latent variable approaches, are delineated.