A large number of diseases/conditions have been found to involve intracellular molecular damage that occurs as a result of hostile, free radical-mediated reactions. Both oxygen and nitrogen-based toxic reactants incessantly mutilate beleaguered, essential molecules, eg, lipids, proteins, DNA, RNA, and so on. The accumulated molecular debris that is a consequence of these reactions could contribute to disease processes and the deteriorative changes of aging. A complex antioxidative defense system has evolved for the purpose of protecting cells from free radicals and the resulting damage. One component of this system is melatonin. This endogenously produced and exogenously acquired (in the diet) indoleamine is a potent direct free radical scavenger and indirect antioxidant (stimulating a variety of antioxidative enzymes). Melatonin has been widely tested to determine its efficacy in protecting against free radical damage in experimental models of heart attack, stroke, Alzheimer disease, Parkinsonism, and others. In these experimental settings, melatonin proved highly effective in reducing molecular damage, cellular death, and tissue loss and, when tested, organismal function was also preserved. In newborn infants with sepsis or respiratory distress syndrome, melatonin was likewise highly effective in limiting the severity of these conditions. Melatonin, which is inexpensive and without significant toxicity, should be considered for more extensive use in humans against free radical-based diseases/conditions.