This article discusses the dual sources of melatonin in mammals, including humans, and their distinct functions. The primary source of melatonin, referred to as Source #1, is the pineal gland. Melatonin production in the pineal gland is circadian, with maximal synthesis and release occurring at night. It plays a key role in regulating the circadian clock, particularly in the suprachiasmatic nucleus (SCN), and in peripheral organs through blood-borne melatonin. The secondary source of melatonin, Source #2, is produced in multiple tissues throughout the body, likely in mitochondria. This source is involved in metabolic regulation and is not circadian, nor is it released into the blood. Instead, it acts locally in the cells of origin and possibly in a paracrine manner on adjacent cells. The regulation of extrapineal melatonin synthesis is not well understood, but it is proposed that melatonin levels are determined by the subcellular redox state and may be inducible under stressful conditions. The article also highlights the role of melatonin in redox homeostasis, antioxidant activity, and its potential therapeutic applications in various diseases. Melatonin is found in a wide range of organisms, including invertebrates, plants, and protists, and its functions are diverse, ranging from protecting against oxidative stress to modulating immune responses. The study emphasizes the importance of both sources of melatonin in maintaining physiological balance and health.This article discusses the dual sources of melatonin in mammals, including humans, and their distinct functions. The primary source of melatonin, referred to as Source #1, is the pineal gland. Melatonin production in the pineal gland is circadian, with maximal synthesis and release occurring at night. It plays a key role in regulating the circadian clock, particularly in the suprachiasmatic nucleus (SCN), and in peripheral organs through blood-borne melatonin. The secondary source of melatonin, Source #2, is produced in multiple tissues throughout the body, likely in mitochondria. This source is involved in metabolic regulation and is not circadian, nor is it released into the blood. Instead, it acts locally in the cells of origin and possibly in a paracrine manner on adjacent cells. The regulation of extrapineal melatonin synthesis is not well understood, but it is proposed that melatonin levels are determined by the subcellular redox state and may be inducible under stressful conditions. The article also highlights the role of melatonin in redox homeostasis, antioxidant activity, and its potential therapeutic applications in various diseases. Melatonin is found in a wide range of organisms, including invertebrates, plants, and protists, and its functions are diverse, ranging from protecting against oxidative stress to modulating immune responses. The study emphasizes the importance of both sources of melatonin in maintaining physiological balance and health.