Unipolar depression is a severe recurrent illness with high lifetime morbidity and premature mortality due to suicide. Numerous double-blind, placebo-controlled trials have shown that lithium is very effective at reducing relapses when given as maintenance therapy. It is also very effective when given as maintenance therapy after electroconvulsive therapy. It can be given once a day at night, and controlled trials have shown a 12-hour plasma lithium level between 0.5 and 0.7 mmol/L the most effective, with very slight side effects. Long-term studies of lithium maintenance therapy show a suicide rate of 1.3 suicides per 1000 patient years. This is much lower than comparative studies in long-term follow-up of untreated depression, which show about 5.5 suicides per 1000 patient years. Although it is neither feasible nor ethical to carry out double-blind studies on suicide reduction, the massive evidence showing a reduction in morbidity on lithium treatment suggests that systematic long-term lithium treatment of unipolar depression could considerably lower the suicide rate.