Anesthesia induction and emergence are critical periods for perioperative safety in the clinic. Traditionally, the emergence from general anesthesia has been recognized as a simple inverse process of induction resulting from the elimination of general anesthetics from the central nervous system. However, accumulated evidence has indicated that anesthesia induction and emergence are not mirror-image processes because of the occurrence of hysteresis/neural inertia in both animals and humans. An increasing number of studies have highlighted the critical role of orexinergic neurons and their involved circuits in the selective regulation of emergence but not the induction of general anesthesia. Moreover, additional brain regions have also been implicated in distinct neural mechanisms for anesthesia induction and emergence, which extends the concept that anesthetic induction and emergence are not antiparallel processes. Here, we reviewed the current literature and summarized the evidence regarding the differential mechanism of neural modulation in anesthesia induction and emergence, which will facilitate the understanding of the underlying neural mechanism for emergence from general anesthesia.