N-Acetylserotonin (NAS) is a naturally occurring chemical intermediate in biosynthesis of melatonin. Previous studies have shown that NAS has different brain distribution patterns from those of serotonin and melatonin, suggesting that NAS might have functions other than as a precursor or metabolite of melatonin. Indeed, several studies have now shown that NAS may play an important role in mood regulation and may have antidepressant activity. Additional studies have shown that NAS stimulates proliferation of neuroprogenitor cells and prevents some of the negative effects of sleep deprivation. It is believed that the antidepressant and neurotrophic actions of NAS are due at least in part to the capability on this molecule to activate the TrkB receptor in a brain-derived neurotrophic factor-independent manner. Emerging evidence also indicates that NAS and its derivatives have neuroprotective properties and protect retinal photoreceptor cells from light-induced degeneration. In this review, the authors discuss the literature about this exciting and underappreciated molecule.