Late-life depression is common in older people. Its incidence increases significantly after age 70 to 85, as well as among those living in long-term care facilities. Depression contributes to excess morbidity and complicates management of comorbid conditions in older people. Diagnosis and management of depression often present clinicians with a challenge. Indeed, symptoms of depression in older people may not always be the same as those associated with depression in younger people. Additionally, age-related changes in pharmacokinetics and pharmacodynamics also impact selection, dosing, and monitoring of psychopharmacologic regimens. Optimizing management of depression and providing sound advice to older patients with depression requires knowledge and understanding of many clinical factors. The purpose of this review is to highlight salient issues in late-life depression, with a focus on the pharmacotherapy of depression.