Preclinical studies have shown that phosphodiesterase inhibitors (PDE-Is) represent a potential pharmacological strategy for the treatment of brain ischemia sequelea. PDE-Is 3, 4 and 5 have been tested in several brain ischemia models. All the three PDE-Is after acute or chronic treatment decreased the degree of neurodegeneration and most of them improved functional recovery after brain injury by specific cellular and molecular mechanisms mainly involving an anti-inflammatory and/or neuroprotection action. In contrast to the large number of investigations using PDE-Is in experimental brain ischemia research, the number of clinical studies is still limited. The purpose of this review is to summarize the data currently available on the effects of PDE-Is in experimental models of cerebral ischemia.