Abstract: Post-stroke depression (PSD) is the most common complication of post-stroke neuropsychiatric disorders with a prevalence of above 40% in patients with stroke in mainland China. PSD has a detrimental impact on the recovery of physical function, cognition and the quality of life in stroke patients, exaggerating the disability and mortality of stroke. However, the pathological mechanism of PSD remains unclear, possibly involving the disturbance of inflammatory immune system, monoamine neurotransmitter system, oxidative stress and neurotrophic factors. It has been found that drug therapy has a benefit effect on the recovery of physical function and cognition in stroke patients with PSD, but the evidence is still insufficient to support the routine drug strategy to prevent PSD. Thus, further research on PSD pathological mechanisms and related biomarker screening will provide a basis for the development of a reasonable drug treatment strategy. In this paper, the potential pathological mechanisms of PSD, the advances of clinical drug treatment and the research progress of PSD biomarkers have been reviewed and summarized.