Neonatal seizure related to stroke is a common diagnostic feature. Their treatment, although widely debated even today must be initiated in case of status epilepticus, clinical seizures of more than 5 minutes duration or short (> 30 secondes) and repeated clinical seizures (2 or more per hour). The treatment of neonatal seizures is a challenge that remains only partially solved. It should take into account the etiology of seizures, type of brain lesions and clinical/electrical response to treatment after the first line treatment. It is based on using a single anti-epileptic at its maximum dosage, and if needed, on the association with another anti-epileptic drug with a different mechanism of action. Phenobarbital remains the most commonly used drug for initial treatment of neonatal seizures and for which the most clinical experience has been accumulated. The lack of randomized controlled trials makes difficult recommendations about the optimal duration of treatment, but most experts agree that once arrested seizures, the duration of treatment should be as short as possible because of its potential risk on the developing brain. Novel neuroprotective strategies for reducing impact of neonatal stroke or promoting brain repair remain for the moment the concept stage, pre-clinical or parcel clinical data.