Functions of the central nervous system (CNS) are based on a complex neural network. It is believed that the CNS has several neuroprotective mechanisms operated by neurons, glia and other types of cells against various types of neuronal damage. Since mature, differentiated neurons are not able to divide, it is important to protect neurons from damage prior to death. The neuroprotective effects of a number of pharmaceutical agents and natural products against necrosis and apoptosis of the CNS neurons have been reported, thus this review will mainly discuss several endogenous neuroprotectants and their mechanisms.