Background Internet support groups (ISGs) enable individuals with specific health problems to readily communicate online. Peer support has been postulated to improve mental health, including depression, through the provision of social support. Given the growing role of ISGs for both users with depression and those with a physical disorder, there is a need to evaluate the evidence concerning the efficacy of ISGs in reducing depressive symptoms.Objective The objective was to systematically review the available evidence concerning the effect of ISGs on depressive symptoms.Method Three databases (PubMed, PsycINFO, Cochrane) were searched using over 150 search terms extracted from relevant papers, abstracts, and a thesaurus. Papers were included if they (1) employed an online peer-to-peer support group, (2) incorporated a depression outcome, and (3) reported quantitative data. Studies included both stand-alone ISGs and those used in the context of a complex multi-component intervention. All trials were coded for quality.Results Thirty-one papers (involving 28 trials) satisfied the inclusion criteria from an initial pool of 12,692 abstracts. Sixteen trials used either a single-component intervention, a design in which non-ISG components were controlled, or a cross-sectional analysis, of which 10 (62.5%) reported a positive effect of the ISG on depressive symptoms. However, only two (20%) of these studies employed a control group. Only two studies investigated the efficacy of a depression ISG and neither employed a control group. Studies with lower design quality tended to be associated with more positive outcomes (P = .07). Overall, studies of breast cancer ISGs were more likely to report a reduction in depressive symptoms than studies of other ISG types (Fisher P = .02), but it is possible that this finding was due to confounding design factors rather than the nature of the ISG.Conclusions There is a paucity of high-quality evidence concerning the efficacy or effectiveness of ISGs for depression. There is an urgent need to conduct high-quality randomized controlled trials of the efficacy of depression ISGs to inform the practice of consumers, practitioners, policy makers, and other relevant users and providers of online support groups.