Post-stroke depression is the most frequent psychiatric complication of stroke. Its prevalence has been estimated to be around 30– 35%, ranging from 20 to 60%, in various studies, depending on the study’ s variables. Stroke patients with post-stroke depression have more severe deficits in activities of daily living, show a minor improvement in rehabilitation programs and a worse functional outcome, more severe cognitive deficits and increased mortality as compared to non depressed stroke patients. Therefore depressed patients have worse functional outcomes and quality of life. The interaction between depression and stroke is very complex and the pathophysiological mechanisms have not as yet been fully elucidated. An interaction between anatomical and psychosocial factors may be important in development of post-stroke depression, and neurochemical changes could be similar to endogenous depression. It seems that post-stroke more often affects female and older stroke patients. There is no agreement on causal mechanisms, risk factors and consequences of PSD, but the available evidence supports PSD as being multifactorial in origin. It seems that the stroke itself poses the risk of depression, because stroke survivors are more prone to depression compared to physically ill patients with similar levels of disability. Diagnosis of PSD is challenging in the acute and chronic aftermath. Therefore, it often remains unrecognized and/or undertreated. Several diagnostic instruments are in use to identify depression in stroke patients, the Montgomery-Asberg-Depression-Rating-Scale, the Geriatric Depression Scale and the Hospital Anxiety and Depression Scale being the most frequently used. Early effective treatment of depression may have a positive effect not only on depressive symptoms but also on the rehabilitation outcome of stroke patients. Randomized controlled trials have demonstrated the efficacy of sertraline, citalopram and nortriptyline in treatment of post-stroke depression. However, it is not clear whether antidepressant medication may help to prevent post-stroke depression and decrease post-stroke mortality. Implementing preventive and therapeutic strategies to reduce the risk of PSD could improve rehabilitation outcomes after stroke.