Post-stroke depression (PSD) is a clinically relevant complication of ischemic and hemorrhagic cerebral infarction that affects about 30% of all stroke survivors. It is associated with reduced quality of life as well as delayed recovery from neurological deficits and functional impairment, frequently leading to impeded rehabilitation. Suitable screening methods allow early detection of PSD. Timely initiation of treatment in patients with manifest PSD as well as implantation of effective prevention strategies can help reduce medical and socioeconomic burden associated with the disease. We reviewed the current literature on pharmacological and non-pharmacological prevention of PSD.