Objective: Identifying mediators of therapeutic change is important to the development of interventions and augmentation strategies. Threat reappraisal is considered a key mediator underlying the effects of cognitive-behavioral therapy (CBT) for anxiety disorders. The present study systematically reviewed the evidence for the threat reappraisal mediation hypothesis. Method: In our review, we included studies that (a) investigated the threat reappraisal mediation hypothesis; (b) included adults with an anxiety disorder diagnosis; (c) used a longitudinal design; and (d) did not report on previously published findings (to avoid the inclusion of multiple reports of the same data). After data extraction, we made review-specific quality judgments for each study using the following a priori criteria informed by mediation theory: (a) demonstrated statistical mediation; (b) demonstrated that CBT caused threat reappraisal; (c) demonstrated that threat reappraisal caused anxiety reduction; and (d) demonstrated specificity of the threat reappraisal-anxiety reduction relation. Results: Of the 2,296 studies we identified, 25 met inclusion criteria. Of these studies, 56% tested and 52% established statistical mediation, 52% tested and 28% established CBT as a cause of threat reappraisal, 28% tested and 24% established threat reappraisal as a cause of anxiety reduction, and 44% tested and 36% established specificity of the threat reappraisal-anxiety reduction relation. Conclusions: While threat reappraisal is related to anxiety symptom improvement with CBT, there are few extant studies that meet most of the criteria necessary to conclusively demonstrate that it causes symptom improvement in CBT and that it is not a proxy for other third variables. Recommendations for future research in this area are discussed. (Contains 2 figures and 2 tables.)