In the mitochondrial electron transport pathway (ET-pathway) electrons are transferred from reduced substrates to oxygen which is coupled to the phosphorylation of ADP to ATP. The electron transfer pathway leads to electron leakage, mitochondria, which is the most important source of free radicals in cells. When mitochondria are damaged by oxidation, they cannot keep up with the cell's energy needs. This determines the cell to produce more free radicals. Both mechanisms, namely faulty ATP generation and elevated oxygen radicals, may promote mitochondrial-dependent apoptosis. Melatonin's high concentrations and diverse antioxidant activities provide substantial protection to organelles which are exposed to a large number of free radicals. It has been shown that melatonin reduces oxidative stress and stress-induced mitochondrial dysfunction both in vitro and in vivo. Moreover, melatonin is protective against a number of illnesses in which excessive free radical production is the primary cause of the disease. Several diseases are characterized by mitochondrial damage caused by oxidative stress. Consequently, melatonin has gained recognition as a potential therapeutic agent for treating cancer and other mitochondrial dysfunctions in cancer cells.