Cerebral hypoxic-ischaemic injury is a significant cause of death and neurological impairment. Magnetic resonance spectroscopy studies have shown that transient hypoxia-ischaemia leads to a biphasic disruption of cerebral energy metabolism. Related to this biphasic energy failure, two waves of cell death seem to follow hypoxic-ischaemic injury in the developing brain. Immediate neuronal death is probably largely due to necrosis, resulting mainly from the accumulation of calcium ions, leading to membrane pump failure.41 Delayed cell death resulting from hypoxic-ischaemic injury seems to involve different or additional mechanisms and a growing body of data suggests that in the delayed phase of injury cell death occurs by apoptosis. In the developing nervous system apoptosis is observed as early as neural tube formation and persists throughout terminal differentiation of the neural network. apoptosis in neural cells. Neurotrophin withdrawal leads to death by a default mechanism through as yet uncharacterised pathways. Gene mutations, inappropriate production of neurotransmitters, such as glutamate, free radical generation, and mitochondrial damage also trigger apoptosis as do engagement of death receptors. In the latter case oligomerisation of Fas/Apo-1 or TNF receptors or the p75 NGF receptor results in the recruitment of death domain proteins, which in turn activate members of the caspase family of cysteine proteases in an organised proteolytic cascade. Bcl-2 family members and inhibitor of apoptosis proteins (IAPs) control the decision to commit cell suicide, depending on whether pro- or anti-apoptotic paners predominate. In the later stages, specific endonucleases cleave DNA as pa of the packaging process. Finally, cells are phagocytosed by healthy neighbours