Over 10% of medically ill elderly persons have concurrent major depression, and medical illness is the most influential stressor contributing to depression in old age. The contribution of prescribed medications to depression in the medically ill is poorly understood. Most information on drug-induced depression is derived from case reports; 43 classes of medications have been implicated, including reserpine, beta-blockers, levodopa, corticosteroids, and antipsychotics. However, large rigorously performed studies of some drugs, particularly antihypertensives, suggest that drug-induced depression is uncommon and idiosyncratic. There is no evidence that age is an independent risk factor for drug-induced depression. However, elderly persons are the largest consumers of prescribed drugs, and the burden of drug-induced depression is carried by the old. Because of the frequency of atypical presentations of mental disorders in the elderly, drug-induced depression is often misdiagnosed. Nevertheless, basic principles of geriatric medicine offer useful guidance to clinicians in evaluating the complex interrelationships between prescribed medications and depression. We recommend an approach that includes regular inquiry into the common symptoms of mood disorders, vigilance in assessing the contribution of drugs in their development, but scepticism in assessing a depressive episode as caused only by medication.