Mitochondria play a central role in the survival and death of neurons. The detailed bioenergetic mechanisms by which isolated mitochondria generate ATP, sequester Ca(2+), generate reactive oxygen species, and undergo Ca(2+)-dependent permeabilization of their inner membrane are currently being applied to the function of mitochondria in situ within neurons under physiological and pathophysiological conditions. Here we review the functional bioenergetics of isolated mitochondria, with emphasis on the chemiosmotic proton circuit and the application (and occasional misapplication) of these principles to intact neurons. Mitochondria play an integral role in both necrotic and apoptotic neuronal cell death, and the bioenergetic principles underlying current studies are reviewed.