We review three studies of omega-3 fatty acids in the treatment of depression that were carried out by our research group at the Beer Sheva Mental Health Center. The first study examined eicosapentaenoic acid (EPA) versus placebo as an adjunct to antidepressant treatment in 20 unipolar patients with recurrent major depression. The second study used omega-3 fatty acids in childhood major depression; 28 children aged 6-12 were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. The third study was an open-label add-on trial of EPA in bipolar depression. Twelve bipolar outpatients with depressive symptoms were treated with 1.5-2.0 g/day of EPA for up to 6 months. In the adult unipolar depression study, highly significant benefits were found by week 3 of EPA treatment compared with placebo. In the child study, an analysis of variance (ANOVA) showed highly significant effects of omega-3 on each of the three rating scales. In the bipolar depression study, 8 of the 10 patients who completed at least 1 month of follow-up achieved a 50% or greater reduction in Hamilton depression (Ham-D) scores within 1 month. No significant side effects were reported in any of the studies. Omega-3 fatty acids were shown to be more effective than placebo for depression in both adults and children in small controlled studies and in an open study of bipolar depression. (This review discusses three studies, all from our group, completed before the clinical trial registry was initiated.)