The full range of physiological actions of melatonin is not completely known. In mammals, it modulates gonadal function and regulates biological rhythms. Furthermore, it has also been reported to have anxyolitic, sedative, and anticonvulsant properties, both in human and animals. Recently it has been shown that melantonin is a potent, endogenous hydroxyl radical scavenger suggesting that it might interfere with neurodegenerative processing involving free-radical formation and excitatory amino acid release. Using primary cultures of rat cerebellar neurons and in vivo models of brain injury in rats, we demonstrate that melatonin might be considered an endogenous neuroprotective factor useful for the pharmacological treatment of neurological disorders and neural degeneration produced by glutamate excitotoxicity and oxidative stress.