Secondary brain injury after hypoxia-ischemia is associated with delayed loss of high energy phosphates implicating bioenergetic mitochondrial failure at least partly related to deregulation of the energy sensor adenosine monophosphate-activated protein kinase. Furthermore, the toxic intracellular environment (accumulation of reactive oxygen/nitrosative species and intracellular calcium) during post-ischemic reperfusion triggers Bax-dependent mitochondrial permeabilization (MP) leading to activation of caspase-dependent and apoptosis-inducing factor dependent cell death. We still do not understand how MP is induced but some data suggest that mitochondrial fusion/fission as well as migration play a critical role. Mitochondrial dynamics also seem critical for brain development as genetic deficiency of proteins involved in mitochondrial fusion and fission results in malformations including microcephaly, abnormal brain development and dysmyelination. In this brief review, we update the critical role of mitochondria in brain development and the decision of cell fate after hypoxia-ischemia in the immature CNS.