Depression occurs in about 15% of the general population and is at least two to three times more common in patients with cancer. Depression is often difficult to diagnose in these patients because of the complexity and constraints of cancer care, patient and family reluctance to acknowledge distress, and the presence of multiple other symptoms. Both antidepressants and psychotherapy are effective in treating depression in patients with cancer, much like in patients with other significant medical problems. Precise assessments of the benefits of treating depression in these patients are important in weighing them against the costs and potential adverse effects. Such estimates are limited by a paucity of randomized, placebo-controlled trials and methodological problems in the existing studies that reflect some of the clinical difficulties in case-finding, treatment, and follow-up of patients with cancer. The existing body of research about depression in cancer patients is extremely limited in terms of the number of studies published and the number of total patients reported over the last 30 years. Moreover, these limited data may not generalize well because of high rates of patient dropout and the very limited enrollment of children, adolescents, older adults, and minority groups. There is an emerging trend toward simplifying the assessment of depression in outpatient cancer care settings and studying depression therapies in cohorts of patients with cancer other than those with fully characterized depressive disorders.