The goals of this meta-analysis are two-fold: (1) to analyze the efficacy of omega-3 fatty acids in the treatment of MDD and (2) to examine possible sources of heterogeneity between trials. We specifically hypothesize that possible sources of heterogeneity include (1)omega-3 fatty acid dose, (2) trial duration, (3) diagnostic heterogeneity, (4) the use of omega-3 treatment as monotherapy vs. augmentation, and (5) baseline depression severity. These sources of heterogeneity represent potentially important differences affecting the efficacy omega-3 fatty acid pharmacotherapy in clinical practice.