A substantial body of research suggests that anesthetic exposure to patients who are very young or very old may impair cognitive, behavioral, and emotional development or recovery. In lower animal models of pre- and postnatal age, anesthetic exposure may impact inflammation, synaptogenesis, neuronal apoptosis, and glial cell development. To date, research in humans is inconclusive regarding the long-term cognitive and behavioral sequelae of general anesthesia in the young child. In older adults, postoperative cognitive dysfunction and cognitive delirium are identified as markers of anesthetic neurotoxicity. Existing neurological degenerative processes and other comorbidities in combination with the stress of surgery make evaluating the independent impact of anesthetic exposure difficult. Advances in research, imaging, and partnerships have enhanced the potential for understanding the impact of anesthetic exposure. In both populations, the resulting data and limitations faced in initial research efforts are catalysts for current prospective studies.