Lipoxygenases are a family of enzymes which dioxygenate unsaturated fatty acids, thus initiating lipoperoxidation of membranes and synthesis of signaling molecules, as well as inducing structural and metabolic changes in the cell. The Lox enzymes in mammals include 12-LO and 15-LO, which are classified with respect to their positional specificity of the deoxygenation of their most common substrate, arachidonic acid. The metabolism of arachidonic acid leads to the generation of biologically active metabolites that have been implicated in cell growth and proliferation, as well as survival and apoptosis. 15-Lipoxygenase (15-LO) acts in physiological membrane remodeling and the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. It is highly regulated and expressed in a tissue- and cell-type-specific fashion. IL-4 and IL-13 play important roles in transactivating the 15-LO gene. Overexpression of 15-LO type 1 in prostate cancer contributes to the cancer progression by regulating IGF-1R expression and activation.