Medical complications after stroke are an important problem not only for patients, but also for their families and the clinicians who take care of them, thus representing a major public health problem. Among medical illnessess complicating stroke, in the last several years much efforts has been directed to determine the role of affective disorders. Although depression coexisting with stroke has been shown to increase levels of functional disability and reduce the effectiveness of rehabilitation, we still have much to learn about the clinical interface between such disorders. This review focuses on the data concerning the potential relationship between depression and cerebrovascular disease (CVD) and the emerging insights which may be relevant to provide directions for the development of novel research strategies on the pathogenesis and treatment of post-stroke depression.