The mechanism of general anesthesia has long been regarded as a core scientific issue in the area of anesthesiology. Because of the similarity in the physiology signs and electroencephalogram patterns during general anesthesia and sleep, particularly the slow‑wave sleep, or non‑rapid eye movement (NREM) sleep, it has long been believed that general anesthesia may engage in the natural sleep‑wake regulation circuits and exert anesthetic effect by acting on the sleep‑wake nucleus, but this opinion is controversial. It is gradually realized that neurons and associated projections of the ventrolateral preoptic area (VLPO) participate in the regulation of sleep and general anesthesia while various neuropeptides and astrocytes contained in VLPO may also play an important role in it. This review aims to summarize the research advances of the neuron types and associated projections of VLPO, which is the key nucleus necessary for sleep initiation. It also focuses on the neural mechanism of regulating sleep‑awake and general anesthesia.