Depression is the most common psychiatric complication after stroke. Its prevalence varies from 20% to 80%, and it is underdiagnosed and undertreated. It has significant impact on rehabilitation, motor recovery, activities of daily living, social and interpersonal life, and mortality. Several studies have shown that biological and psychosocial factors play significant roles in the development of this disabling disease. Recent research shows that neurochemical processes also may play some role in the pathophysiology of this condition. Several trials have shown evidence that the older, as well as newer antidepressants and psychostimulants may reduce/prevent depressive symptoms after stroke. At this point there are no clear guidelines available to choose safe and effective treatments. Drugs are selected based on their efficacy and side effect profile in these patients. More research is needed to understand the pathophysiology of depression after stroke. There also is a need for more randomized clinical trials to better treat patients with this condition.