Sleep-wake regulation is a core physiological process dominated by widely distributed neural circuits in the brain. In recent years, with the development of optogenetics and chemogenetics technologies, researchers have not only improved their understanding of the functions of multiple classic regulatory brain regions (such as the reticular activating system, thalamus, hypothalamus, and basal forebrain) but also successively identified and verified a series of novel sleep-wake regulatory nuclei. These studies have simultaneously revealed the regulatory roles of various neurotransmitters, including histamine (HA), dopamine (DA), orexin, γ-aminobutyric acid (GABA), and norepinephrine (NE), in the sleep-wake process, laying a theoretical foundation for deciphering the mechanisms of sleep-wake-related neural circuits. This article systematically reviews the research progress on the neural mechanisms of sleep-wake regulation, explores its intervention targets, and provides a theoretical basis for the development of novel wake-promoting drugs. Regarding therapeutic targets, drugs such as histamine H3 receptor antagonists (e.g., pitolisant), dopaminergic modulators (e.g., modafinil, solriamfetol), orexin type 2 receptor agonists (e.g., TAK-861), GABA B receptor agonists (e.g., sodium oxybate), and NE reuptake inhibitors (e.g., AXS-12) have shown broad clinical application prospects in promoting wakefulness. Although the development of wake-promoting drugs still faces challenges such as hepatotoxicity, significant individual differences in efficacy, and lack of long-term safety data, with the deepening understanding of the mechanisms of sleep-wake-related circuits, precise intervention strategies targeting specific neurotransmitter systems are expected to open up new avenues for the treatment of sleep-wake disorders.