To counteract excitotoxic mechamisms involved in a great deal of acute and chronic neurodegenerative disorders, efforts have been addressed, over the last decade, to search for drugs that either reduce glutamate synaptic levels or block its postsysnaptic effects. Among the large amount of compounds tested, riluzole and the NMDA receptor antagonist memantine have proved to be quite efficacious in amyotrophic lateral sclerosis and in Alzheimer, disease respectively. Other clinical trials of antiexcitotoxic agents have been unsuccessful, despite the encouraging data collected in animal models, probably because of methodological or dosage problems. Moreover, some of these drugs might increase their efficacy if administred in early stages of disease and in combination with other neuroprotective agents, such as antioxidants and antiapoptotic substances.