Arachidonate 12-lipoxygenase introduces a molecular oxygen at carbon 12 of arachidonic acid to generate a 12-hydroperoxy derivative. The enzymes generate 12-hydroperoxy derivatives with either S- or R-configurations. There are three isoforms of 12S-lipoxygenases named after the cells where they were first identified; platelet, leukocyte and epidermis. The leukocyte-type enzyme is widely distributed among cells, but the tissue distribution varies substantially from species to species. The platelet and epidermal enzymes are present in only a relatively limited number of cell types. Although the structures and enzymatic properties of the three isoforms of 12S-lipoxygenases have been elucidated, the physiological roles of the 12S-lipoxygenases are not yet fully understood. There are important roles for the enzymes and their products in several biological systems including those involved in atherosclerosis and neurotransmission.