The circadian clock is involved with many aspects of biological processes in animals and plants. Melatonin is a pineal hormone which is known to play a widespread role in the biochemistry of the circadian clock. The present review addresses the clock and melatonin in relation to aging and cancer, which are important aspects of medicine and biochemistry. The literature contains a large variety of associations of these areas with melatonin and circadian rhythm. Mechanistic aspects are addressed with emphasis on the unifying theme based on electron transfer-free radicalsoxidative stress.