Cerebrovascular diseases constitute a leading health hazard. The association between stroke and depression has been recognized for many years. Depression is the most common psychiatric disorder associated with cerebrovascular diseases, most episodes of post-stroke depression occur in the first 2 years after a cerebrovascular accident. Studies have found an association between lesion location, physical impairment, cognitive impairment, aphasia, and post-stroke depression. The location of the lesion in terms of proximity to the left frontal pole of the brain has a profound impact on the frequency and severity of post-stroke depression. Treatment modalities include pharmacotherapy, psychotherapy, electroconvulsive therapy, and rehabilitation. Understanding the psychologic and physical morbidity of post-stroke depression, as well as its timely, comprehensive treatment, are important for effective management.