The liver X receptors (LXRs), LXRalpha and LXRbeta, are ligand-activated transcription factors of the nuclear receptor superfamily that control the expression of genes involved in cholesterol and fatty acid metabolism. While the identification of small-molecule non-steroidal LXR agonists has validated the LXRs as potential drug targets for cardiovascular disease, recent reports from several research groups suggest that LXR ligands will be valuable therapeutic agents for the treatment of inflammation, diabetes and neurodegenerative diseases. This review focuses on the effects of LXR agonists on relevant signaling pathways, the recently reported ligand-bound LXR crystal structures, and recently disclosed LXR small-molecule templates.