Depression is an important complication of stroke. Although antidepressants are widely used for the treatment of poststroke depression (PSD), prescription is critically influenced by their safety, tolerability and by the impact on co-morbidities. The authors reviewed the literature on the use of antidepressants after stroke. Selective serotonin re-uptake inhibitors are effective and have a good profile of safety and tolerability in PSD. They are, therefore, used as first-line drugs in the treatment of PSD, although potential cardiovascular and cerebrovascular effects, drug-drug interactions and intolerability in a minority of patients have to be considered. Other antidepressants appear to be safe and effective in selected patients. PSD patients should be classified according to their clinical profile for the selection of the drug of choice in particular sub-groups of patients.