General anesthesia is a crucial supporting strategy for surgical operations and other invasive examinations. Despite the widespread application of general anesthetics, the neurobiological mechanisms underlying general anesthetics' complex multidimensional effects remain ambiguous. This article provides a brief history of the development of general anesthesia, a systematic review of commonly used techniques for systematic dissection into its brain mechanisms, the possible neural circuitry and molecular substrates underlying general anesthesia, and further proposes possible future research directions and challenges.