OBJECTIVE: Of the 34 million adult Americans (17%) using mind-body medicine therapies, 8 million (24%) have anxiety/depression. The evidence for using mind-body therapies to address varying depressive symptoms in populations with and without other chronic comorbidities is reviewed. METHODS: Systematic literature searches of PubMed (Medline), Embase, CINAHL, and the seven databases encompassed by Current Contents, Web of Science, and Web of Knowledge were conducted. Studies designed as prospective control-comparison, adult population, English, at least 2 weeks long, sample size >30, and with primary or secondary outcome as depression measured on an established scale were included. Methodologic quality was evaluated using the modified scale for assessing scientific quality of investigations (SASQI) for Complementary and Alternative Medicine (CAM). RESULTS: Ninety papers of about 2900 met both inclusion and exclusion criteria; 60% of them scored a SASQI >9 and were deemed of sufficient quality to be included in the review; 74% of these selected quality papers demonstrated positive effects on the improvement of depressive symptoms. All mind-body modalities included in the study had at least one positive study. For cancer patients, several studies noted the positive effects of yoga and combination therapies on depression severity. For both diagnosed depression and fibromyalgia, several studies noted the positive effects of mindfulness on depression severity. CONCLUSION: The use of evidence-based mind-body therapies can alleviate depression severity. They could be used with established psychiatric treatments of therapy and medications. The likely long-term increased cost-effectiveness of integrating these therapies deserves further investigation.