Acute neurological conditions such as cerebrovascular diseases and trauma are associated with irreversible loss of neurons and glial cells. Severe or prolonged injury results in uncontrollable cell death within the core of lesions. Conversely, cells that are less severely damaged succumb in a relatively slow fashion, frequently via the intrinsic pathway of cell death, through the deterioration of mitochondrial functions. The permeabilization of mitochondrial membranes determines whether cells will succumb to or survive the injury, and represents a 'point of no return' in mitochondrial cell death. It is therefore an attractive target for the development of new neuroprotective interventions.