Anesthesia facilitates surgery in millions of young children every year. Structural brain abnormalities and functional impairment observed in animals has created substantial concerns among clinicians, parents, and government regulators. Clinical studies seemed ambivalent; it remains unclear whether differential species effects exist towards anesthetic exposure. The current literature search and analysis attempts to unify the available clinical and animal studies, which currently comprise of > 530 in vivo animal studies and > 30 clinical studies. The prevalence of abnormalities was lowest for exposures < 1 hour, in both animals and humans, while studies with injurious findings increased in frequency with exposure time. Importantly, no exposure time, anesthetic technique, or age during exposure was clearly identifiable to be entirely devoid of any adverse outcomes. Moreover, the age dependence of maximum injury clearly identified in animal studies, combined with the heterogeneity in age in most human studies may impede the discovery of a specific human neurological phenotype. In summary, animal and human research studies identify a growing prevalence of injurious findings with increasing exposure times. However, the existing lack of definitive data regarding safe exposure durations, unaffected ages, and non-injurious anesthetic techniques precludes any evidence-based recommendations for drastically changing current clinical anesthesia management. Animal studies focusing on brain maturational states more applicable to clinical practice as well as clinical studies focusing on prolonged exposures during distinct developmental windows of vulnerability are urgently needed to improve the safety of perioperative care for thousands of young children requiring life-saving and quality of life-improving procedures daily.