Depression in older adults is a mood disorder associated with physical and/or cognitive impairment. Though it may be present in a variety of settings, depression is a prominent health concern among long-term care and nursing facility residents. Pharmacologic therapy may be considered in patients with depression who have not responded to nonpharmacologic therapy or are experiencing considerable disability. There are a variety of commonly prescribed antidepressant drug options for this indication. Examples may include selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, or serotonin modulators. As the use of these agents continues in older adults, senior care pharmacists should be familiar with the evaluation of its safe and combined use (e.g., drug interactions, adverse effects).