This chapter reviews the neural connections between the retinas and the pineal gland and summarizes the role of the light:dark cycle and the biological clock, i.e. the suprachiasmatic nuclei, in regulating pineal melatonin synthesis and secretion. The cellular mechanisms governing the nocturnal production of melatonin are described together with the way in which the misuse of light interferes with the circadian melatonin cycle and the total quantity of the indole generated. The chapter describes the nature of the membrane melatonin receptors and their signal transduction mechanisms in peripheral organs. The clinical implications and potential uses of melatonin in terms of influencing the biological clock (e.g. sleep and jet lag), immune function, and cancer initiation and growth are noted. Additionally, the chapter includes a description of the newly discovered free radical scavenging and antioxidant activities of melatonin; it also includes a list of clinical situations in which melatonin has been used with beneficial effects.