The Liver X receptors (LXRs), members of the nuclear receptor superfamily, play an important role in controlling lipid homeostasis by activating several genes involved in reverse cholesterol transport. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apoE, and cholesterol ester transport protein (CETP). LXRs also play an important role in fatty acid metabolism by activating the sterol regulatory element-binding protein 1c gene (SREBP1c). hLXRα itself is an autoinducible gene, and ”auto-induction“ in response to LXR ligands is observed in multiple human cell-types including macrophages. Based on their ability to induce reverse cholesterol transport LXRs appear to be useful and novel targets for the treatment of atherosclerosis, one of the most fatal diseases in the western world. In this article, we review the biological functions of LXRs and discuss the possibility of identifyi ng LXR ligands as drugs for the treatment of atherosclerosis.