This chapter deals with chronotherapeutics and discusses light therapy, wake therapy, and melatonin. Light therapy is the first somatic antidepressant treatment to have been born of a biological hypothesis rather than discovered by serendipity in the course of drug testing or brain stimulation. A single cycle of triple chronotherapy can produce such rapid improvement that after a few more days of observation the patient can be discharged. Others may need a second or third cycle of wake therapy, but the expected course of acute treatment can be completed within a week. Pineal melatonin is produced on a nocturnal cycle triggered by the internal circadian clock, which in turn is synchronized to the day/night cycle by appropriately timed light exposure. The endogenous melatonin cycle is intimately connected to the day/night pattern of light exposure, and thus to light therapy.