Agmatine is a naturally occurring guanidino compound, found in bacteria and plants, with several proposed nervous system-related functions suggestive of beneficial effects in central nervous system injury. Here evidence is presented that agmatine can exert potent neuroprotection in both in vitro and in vivo rodent models of neurotoxic and ischemic brain injuries. The cumulative evidence lead us to suggest that agmatine, a relatively nontoxic compound, be tried for potential therapeutic use after neurotrauma and in neurodegenerative disorders.