Post-stroke depression (PSD) is the most frequent psychiatric complication of stroke. Its prevalence has been estimated to be around 30-35%, ranging from 20 to 60%. Despite the extensive literature on this topic, there is no agreement on causal mechanisms, risk factors and consequences of PSD. Stroke patients with PSD suffer higher mortality rates and show a minor improvement in rehabilitation programs in comparison to non depressed stroke patients. Consequently, they have worse functional outcomes and quality of life. The available evidence supports PSD as being multifactorial in origin, and consistent with the biopsychosocial model of mental illness. Nonetheless, the stroke itself poses the risk of depression. Stroke survivors are more predisposed to PSD compared to physically ill patients with similar levels of disability, even quite a long time after the stroke, regardless of other risk factors. Early effective treatment of depression may have a positive effect not only on depressive symptoms but also on the rehabilitation outcome of stroke patients. On the other hand, there is no definitive evidence that antidepressants or psychotherapy are useful to prevent depression. Implementing preventive and therapeutic strategies to reduce the risk of mood alteration and thus improve rehabilitation outcomes would appear important in the organization of stroke services.