Prevalence of cerebral palsy enhanced dramatically during the last decades in some western countries. Pathophysiology of perinatal brain lesions has been revisited. Etiology seems multifactorial including perfusion failure/hypoxia, preconceptional factors, thyroid hormone and growth factors deficiencies, maternal infections with production of cytokines. Excitatory amino acids and excitotoxic cascade seem to be a common final pathway leading to neural cell death. Pharmacological tools destined to inhibit the excitotoxic cascade have been recently developed and are promising for neonatal "neuroprotection".