BACKGROUND Complementary and alternative medicine (CAM) therapies are used more than conventional therapies by people with self-defined anxiety and depression. Preliminary evidence supports a hypothesis that low plasma concentration of essential fatty acids is associated with depression. Reported here is the result of a systematic review examining the therapeutic efficacy of essential fatty acids for depression. METHODS Data sources included Medline, Psychinfo, AMED (Allied and Complementary Medicine), and Cochrane Controlled Trials Register databases searched from inception through September 2001. English language randomized controlled trials, controlled clinical trials, intervention studies, case control studies, reviews, and case reports of humans were selected, without limits for demographics or co-morbidities. Two abstractors independently evaluated each study, then reconciled findings. When possible, between group treatment effect size was noted or calculated. RESULTS Six articles met inclusion criteria: one RCT, two reviews, and three case control trials. A common outcome measure among the case control trials allowed for direct comparison of effect sizes. CONCLUSIONS The evidence implies promise of a treatment effect of omega-3 fatty acids for depression in adults; although a statement of definitive clinical efficacy is premature. Further study of essential fatty acids as independent and adjuvant therapy for adult depression is indicated, including more sophisticated investigation of dose-response in particular populations.