General anesthesia is necessary for patients to undergo surgery and invasive procedures. However, numerous preclinical studies have demonstrated widespread developmental neurotoxicity of the commonly used anesthetics and sedatives for the immature brain. Clinical studies also suggest a strong correlation between childhood anesthesia exposure and subsequent behavioral or cognitive impairment in adulthood. These findings have attracted increasing attention of anesthesiologists, pediatricians, and caregivers about the safety of anesthesia exposure in children, especially during early childhood. Herein, the aim of this review was to present the molecular mechanism of general anesthesia and its effects on the developing brain and introduce the recent clinical evidence of changes in cognition function post-childhood general anesthesia exposure. More importantly, some of the spots will be importantly discussed to scrutinize the phenomena; only in this way, it may help minimize or eliminate relevant risk factors.