Major depression is a prevalent condition that causes significant morbidity and mortality. Diagnosis may be complicated in depressed patients who offer a medical symptom as their chief complaint. Once the diagnosis is established, treatment is relatively straightforward. In prescribing an antidepressant, consideration should be given to the patient's previous response to medications, the documented efficacy of various agents, their side-effect profiles, and their potential for toxicity. Although the more severe and complicated cases should be referred to a psychiatrist, most depressed patients can be treated by their primary care physician.