The liver X receptors (LXRs), that are nuclear receptors activated by oxysterols, play central roles in the transcriptional control of cholesterol metabolism and function as the sensors of cholesterol homeostasis. In addition, LXRs have also been found to modulate lipogenesis, carbohydrate metabolism, innate immune and inflammatory responses in macrophages. Hence, the ability of LXRs to integrate metabolic and inflammatory signaling makes them particularly attractive targets for intervention in human atherosclerosis, hypercholesterolemia and type 2 diabetes.