Objective: Essential polyunsaturated (omega-3 and omega-6) fatty acids have been proposed to play a role in the aetiology of mood disorders. However, a systematic review of observational studies has not yet been conducted. Therefore, our aim was to conduct a systematic review of the studies which have investigated the relationship between essential fatty acids and mood in the past 15 years. Methods: Four databases (EMBASE, MEDLINE, PsycINFO and ISI Web of Science) were searched for human observational studies of the relationship between essential fatty acids and mood that were published between 1995 and 2009. Results: The search yielded a total of 77 papers which met the inclusion criteria. Many of the studies were small, and the methods heterogeneous. Of the studies which investigated dietary fish intake and mood, 75% found a benefit. While 69% of the dietary intake studies observed an inverse relationship between mood and n-3 intake, 82% of the studies which investigated n-3 biomarker status and mood supported a significant inverse association between these two factors. Conclusions: The findings of the present review suggest that omega-3 fatty acids are potentially beneficial in enhancing mood and reducing the symptoms of mood disorders (including major depression and bipolar disorder), however the heterogeneity with respect to the methodologies employed by studies in the area renders it difficult to draw absolute conclusions. Further longitudinal studies are warranted in order to determine causality. Dietary fish intake appears to be beneficial in terms of enhancing mood.