Poststroke depression (PSD) is a frequent complication and source of suffering among stroke survivors. Assessment of mood, suicidal ideation, and other neuropsychiatric disturbances that can co-occur or share similar features with depression are important aspects of clinical stroke care. Pharmacotherapy is the first-line treatment of PSD, with selective serotonin reuptake inhibitors (SSRIs) being agents of first choice. The evidence for SSRIs, newer generation antidepressants, and tricyclic antidepressants for PSD will be reviewed with consideration of their side effect profiles and use for other neuropsychiatric comorbidities. Additional therapeutic options, such as cognitive enhancing medications, brain stimulation, and psychotherapy can also be considered. Given the prevalence of PSD, preventive pharmacologic strategies may be effective alternatives. Ultimately, the choice of treatment will be determined by the type and severity of medical and psychiatric comorbidities as well as the preferences of the patient.