Neurons vary widely in shape, size, type of neurotransmitters and number of synapses. Their common characteristic is a very high sensitivity to changes in oxygen concentration. The consequence of hypoxia is to launch a series of biochemical reactions called the ischemic cascade. The term is a bit misleading, because it suggests that there is a succession of events, in a linear fashion. In fact, the ischemic cascade involves very complex processes that take place simultaneously and interact with each other. The key role in neuronal responses to hypoxia is played by changes related to mitochondria, which occur immediately after hypoxia, at the beginning of the ischemic cascade. Disturbances in the mitochondrial functions are recognized as an essential element not only in acute but also in chronic hypoxia, as well as neurodegenerative diseases.