Melatonin is a multitasking molecule with sleep-promoting, cancer-inhibiting, anti- inflammatory and antioxidative actions. The objective of this presentation is to summarize the published literature in reference to the antioxidant properties of the indoleamine. The function of antioxidants is to neutralize toxic free radicals, many of which are derivatives of molecular oxygen, before they inflict damage (oxidative stress) to essential macromolecules. This molecular mutilation contributes to many diseases and is a major aspect of age-related deterioration. Using a combination of fluorescence microscopy, cyclic voltammetry, high performance liquid chromatography, mass spectrometry, electron spin resonance spectroscopy and nuclear magnetic resonance, melatonin was proven to be a potent free radical scavenger, including a high efficiency in scavenging the devastatingly toxic hydroxyl radical and the peroxynitrite anion. Moreover, metabolites of melatonin that are formed when it scavenges radicals, i.e., cyclic 3- hydroxymelatonin, N1-acetyl-N2-formyl-5- methoxykynuramine (AFMK) and N1-acetyl-5- methoxykynuramine (AMK) are also effective scavengers. The series of reactions whereby melatonin and its metabolites neutralize free radicals and associated reactants is referred to as melatonin's antioxidant cascade. A major site of intracellular free radical generation is the respiratory chain in the inner mitochondrial membrane. Melatonin accumulates in mitochondria where it detoxifies free radicals shortly after they are generated. In conclusion, in vivo melatonin has been shown to efficiently protect essential molecules from oxidative damage thereby contributing to disease prevention, especially diseases associated with advanced age.