Liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Two LXRs (LXRalpha and LXRbeta) were initially characterized as orphan members of this superfamily with disparate patterns of tissue expression. These two receptors later were recognized as sterol-responsive with the ability to directly bind several oxysterol metabolites. Many LXR target genes have been identified that implicate these receptors in a variety of physiological processes including cholesterol transport and metabolism, glucose metabolism, and inflammation. Synthetic LXR ligands have been designed with the potential to treat disorders such as atherosclerosis and diabetes. In this review, we describe the potential utility of LXR ligands in the treatment of disease.