During perinatal asphyxia several mechanisms aim to limit cerebral damage. However, when the degree of asphyxia passes beyond a certain threshold, brain damage is inevitable. This review focuses on the various factors determining the final cerebral outcome. Metabolic and biochemical events, such as the intracellular level of calcium, the formation of oxygen derived free radicals, the release of excitotoxic neurotransmitters and the interrelationship of these parameters are discussed. Furthermore, steps possibly useful to pharmacologic intervention aiming to reduce cerebral damage are presented.