Anesthesia kills neurons in the brain of infantile animals, including primates, and causes permanent and progressive neurocognitive decline. The anesthesia community and regulatory authorities alike are concerned that is also true in humans. In this review, I summarize what we currently know about the risks of pediatric anesthesia to long-term cognitive function. If anesthesia is discovered to cause cognitive decline in humans, we need to know how to prevent and treat it. Prevention requires knowledge of the mechanisms of anesthesia-induced cognitive decline. This review gives an overview of some of the mechanisms that have been proposed for anesthesia-induced cognitive decline and discusses possible treatment options. If anesthesia induces cognitive decline in humans, we need to know what type and duration of anesthetic is safe, and which, if any, is not safe. This review discusses early results of comparative animal studies of anesthetic neurotoxicity. Until we know if and how pediatric anesthesia affects cognition in humans, a change in anesthetic practice would be premature, not guided by evidence of better alternatives, and therefore potentially dangerous. The SmartTots initiative jointly supported by the International Anesthesia Research Society and the Food and Drug Administration aims to fund research designed to shed light on these issues that are of high priority to the anesthesia community and the public alike and therefore deserves the full support of these interest groups.