Post-stroke depression (PSD) has been recognized for over a century but systematic studies began in the 1970s. Meta-analyses have emerged due to the small patient numbers in some stroke studies, often merging patients with mood disorders and those scoring above cutoff points on depression scales, missing important findings like cognitive impairment. PSD occurs in a significant number of patients, leading to increased disability and mortality. Recent meta-analyses show the efficacy of antidepressants in treating PSD and preventing its onset. Early antidepressant treatment enhances physical and cognitive recovery and may increase survival up to 10 years post-stroke. Inflammatory processes, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission are potential etiological factors. Further research is needed to understand specific symptoms and clinical characteristics of PSD to develop targeted treatments.Post-stroke depression (PSD) has been recognized for over a century but systematic studies began in the 1970s. Meta-analyses have emerged due to the small patient numbers in some stroke studies, often merging patients with mood disorders and those scoring above cutoff points on depression scales, missing important findings like cognitive impairment. PSD occurs in a significant number of patients, leading to increased disability and mortality. Recent meta-analyses show the efficacy of antidepressants in treating PSD and preventing its onset. Early antidepressant treatment enhances physical and cognitive recovery and may increase survival up to 10 years post-stroke. Inflammatory processes, genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission are potential etiological factors. Further research is needed to understand specific symptoms and clinical characteristics of PSD to develop targeted treatments.