Millions of human fetuses, infants, and children are exposed to anesthetic drugs every year in the United States and throughout the world. Anesthesia administered during critical stages of neurodevelopment has been considered safe and without adverse long-term consequences. However, recent reports provide mounting evidence that exposure of the immature animal brain to anesthetics during the period of rapid synaptogenesis, also known as the brain growth spurt period, triggers widespread apoptotic neurodegeneration, inhibits neurogenesis, and causes significant long-term neurocognitive impairment. Herein, we summarize currently available evidence for anesthesia-induced pathological changes in the brain and associated long-term neurocognitive deficits and discuss promising strategies for protecting the developing brain from the potentially injurious effects of anesthetic drugs while allowing the beneficial actions of these drugs to be realized.