Undesired weight gain is a common complaint of patients receiving pharmacological treatment for major affective disorders. It has been found to jeopardize patient compliance and may pose additional health hazards. A review of the literature on weight gain associated with tricyclic antidepressants, monoamine oxidase inhibitors, and lithium was carried out with the aim of deriving practical management strategies. Tricyclic antidepressants were found to stimulate appetite, carbohydrate craving, and a dose-dependent continuous weight gain of 0.57 to 1.37 kg per month of treatment. Proposed mechanisms include noradrenergic or antihistaminic inhibition of satiety and decreased metabolic rate. Novel serotonergic and dopaminergic antidepressants were found to be anorectic. Monoamine oxidase inhibitors may stimulate appetite and potentiate insulin-induced hypoglycemia. Lithium maintenance therapy stimulates weight gains of over 10 kg in 20% of patients. Documented mechanisms include insulin-like actions on carbohydrate and fat metabolism, polydipsia, and sodium retention. Recommendations regarding choice of antidepressant drug as well as dietary and behavioral strategies to prevent excessive weight gain are presented. Potential adjunctive drug approaches to severe weight gain are reviewed.