In recent years, post-stroke depression (PSD) has attracted a worldwide interest. This review addresses the major research issues of PSD. PSD is the most frequent psychic complication among stroke survivors. Depression has a significant impact on post-stroke recovery and mortality. The diagnosis of PSD is based on the structured mental state examination and DSM-IV criteria as well as on the scores of the clinical symptoms scale (the Hamilton Depression Rating Scale) and self-rated inventories. PSD is multifactorial in origin and develops under the influence of biopsychosocial factors. The anatomical correlates of PSD change over time. In acute stage and 3-6 months after stroke, depression is associated with left-hemisphere lesion severity and proximity of the lesion to the frontal pole and related to the dysfunction of (cortico-) striato-pallido-thalamic-cortical projections. In post-stroke period (1-2 years) depression is significantly associated with right-hemisphere lesion severity and proximity of the lesion to the occipital pole. The most relevant psychosocial risk factors for PSD are described as follows: past history of depression and other mental disorders, dysphasia, functional impairment, living alone and post-stroke social isolation. Selective serotonin reuptake inhibitors (citalopram and fluoxetine) may be effective in the treatment of PSD.