Perinatal stroke represents an important cause of severe neurological deficits that span the individual's lifetime, including delayed mental and motor development, epilepsy and major cognitive deficits. Most strokes occurring in term births, infants and children can be caused by thromboembolism from intracranial and extracranial vessels and are associated with a variety of risk factors such as birth asphyxia, cardiac diseases, blood disorders, maternal disorders, trauma. Animal models of perinatal stroke have been developed to examine the nature and the time course of the events occurring after the ischemic insult and the possible therapeutic strategies useful in reducing ischemic damage. The present article addresses the potential pharmacological treatments targeting the inflammatory process and apoptotic cell death, with a specific emphasis on the emerging role of statins as neuroprotective agents in perinatal stroke. As a prelude, we will also review advances in our understanding on the mechanisms underlying the hypoxic-ischemic reperfusion injury in the newborn.