Depression is a common occurrence after stroke and is associated with excess disability, cognitive impairment, and mortality. The authors undertook a systematic review of the English language literature to review several aspects of this illness, including the prevalence of this disorder, the debate on its etiology, and the current understanding of the biological treatment of poststroke depression. Methodological problems encountered in the study of poststroke depression are highlighted throughout the manuscript. The authors conclude that the available evidence supports poststroke depression as being multifactorial in origin and consistent with the biopsychosocial model of mental illness.