ABSTRACT: Liver X receptors (LXRa and LXRb) are members of the nuclear hormone receptor super family and are involved in the regulation of cholesterol and lipid metabolism. They are ligand-activated transcription factors and bind to DNA as obligate heterodimers with retinoid X receptors. In macrophages, liver, and intestine, activation of LXRs induce the expression of several genes involved in lipid metabolism and reverse cholesterol transport including ABCA1, ABCG1 and ApoE. The potential to prevent or even reverse atherosclerotic process by increasing the expression of these genes makes LXR an attractive drug target in the treatment of atherosclerosis which is one of the leading health concerns in the United States. Currently available synthetic LXR pan agonists, however, lead to the undesired activation of triglyceride (TG) synthesis in the liver by the upregulation of SREBP-1c and FAS. Since the liver contains predominantly LXRa, then LXRb selective agents may have less impact on TG synthesis. However, LXRb may be effective in macrophage reverse cholesterol transport. The synthesis, SAR and biological activity of benzylamine based quinolines designed to be LXRb-selective modulators will be described.