Ischemic neuronal injury is characterized by early death mediated by excitotoxicity and by delayed death caused by apoptosis. Current evidence indicates that volatile agents, barbiturates, and propofol can protect neurons against ischemic injury caused by excitotoxicity. In the case of volatile agents and propofol, neuroprotection may be sustained if the ischemic insult is relatively mild; however, with moderate to severe insults, this neuronal protection is not sustained after a prolonged recovery period. This suggests that volatile agents and propofol do not reduce delayed neuronal death caused by apoptosis. The long-term effects of barbiturates on ischemic cerebral injury are not yet defined. Cerebral ischemia is characterized by continued neuronal loss for a long time after the initial ischemic insult. Therefore, in investigations of cerebral ischemia, the duration of the recovery period should be taken into consideration in the analysis of the neuroprotective effects of anesthetic agents. A combination of different approaches that target specific stages of the evolution of ischemic injury may be required for sustained neuroprotection.