This chapter examines the bidirectional relationship between depression and stroke. It is now clearly established that depression is a significant risk factor for stroke, and vice-versa. We review the main biological and demographic factors underlying the association between stroke and depression, the predicted mortality, the mechanism of post-stroke depression, and recent findings on its pharmacological prevention. We conclude by stressing the need for developing effective strategies to manage the burden of illness associated with these interacting conditions. As with the cardiovascular system depression has major effects on the occurrence of stroke. Morbidity and mortality are increased for patients with cerebral vascular accidents (CVA) who are depressed and is seen even in a 10-year follow-up. Depression should be treated concurrently with the management of the acute phase of a CVA.