Neuronal death after ischemic or traumatic injury is mediated, in large part, by excitotoxicity. Originally, it was thought that cell damage by ischemia/reperfusion and other forms of neuronal insults was caused by calcium-mediated activation of phospholipases and proteases, leading to release of free fatty acids and their metabolites, the concomitant generation of reactive oxygen species, and the degradation of cytoskeletal proteins. In an effort to limit the formation of reactive oxygen species in human disease and provide functional sparing of brain tissue, pharmaceutical research in the past focused on the development of free-radical scavengers (1). Unfortunately, many of these approaches were met with disappointment. From recent studies, it is now clear that an important coupling exists between glutamate release, calcium influx, and enhanced production of reactive oxygen species, such as superoxide anion, hydrogen peroxide, hydroxyl radical, and nitric oxide (NO). Of these reactive oxygen species, recent efforts have focused on the reaction product of NO and superoxide anion, peroxynitrite (ONOO−), an oxidant with potentially devastating cellular effects. Drug development has concentrated primarily on strategies to limit ONOO− formation by developing NO synthase (NOS) inhibitors (2) or superoxide dismutase mimetics (3). Discoveries in this area leading to potentially therapeutically useful agents have also been a disappointment. Chabrier et al. (4) report a bifunctional agent, BN 80933, which exerts the dual effect of inhibition of NO formation and scavenging of reactive oxygen species. BN 80933 provides significant neuroprotection even when administered after the neurologic insult.