Major recurrent affective disorders, including major depressive disorder (MDD) and bipolar disorder, represent a growing public health crisis in the United States. Evidence from cross-national and cross-sectional epidemiological surveys, comparative peripheral and central composition studies, and placebo-controlled intervention trials suggest that n-3 fatty acid deficiency may contribute to the pathoaetiology of affective disorders. These data are reviewed with the objective of estimating a daily docosahexaenoic acid (DHA, 22:6n-3) intake value that is projected to be efficacious in mitigating vulnerability. It is proposed that daily DHA intake sufficient to increase erythrocyte DHA composition to a level found in healthy subjects from Japan (7%), where the lifetime prevalence rates of MDD and bipolar disorder are several fold lower than the US, represents an appropriate target. To achieve this target, preliminary DHA intervention trials indicate that a daily dose of 400-700 mg/d in children and 700-1000 mg/d in adults would be required. Based on the results of placebo-controlled intervention trials, a higher daily DHA dose in the order of 1000-1500 mg/d in a 2:1 eicosapentaenoic acid (EPA, 20:5n-3):DHA ratio may be optimal for the treatment of established affective disorders. These recommendations are intended to guide future dose-ranging placebo-controlled DHA intervention trials in patients with established affective disorders, as well as in asymptomatic subjects at elevated risk for developing affective disorders. Such early intervention studies are currently feasible and will ultimately be required to definitively evaluate whether DHA is a required nutrient for the prevention of affective disorders.