Although numerous second-generation isoprenylation inhibitors are proposed or under investigation for the treatment and/or prevention of cancer (eg, R115777, SCH 66336, L-778,123, BMS-214662), the chemotherapeutic and chemopreventive potential of commonly prescribed first-generation isoprenylation inhibitors, the statins, and other classes of lipid-lowering medications, the fibrates, has yet to be seriously explored. Two lipid-lowering medications, lovastatin and gemfibrozil, have been associated with a decreased incidence of melanoma in large, prospective, randomized, double-blind, placebo-controlled clinical cardiology trials. This article reviews melanoma biology and the clinical evidence for the use of lipid-lowering medications for melanoma chemoprevention and/or adjuvant chemotherapy.