Liver X receptors (LXRs) are cholesterol-sensing nuclear receptors that are not only key regulators of lipid metabolism and transport but also suppress inflammatory signaling in macrophages through a unique mechanism of transrepression. In this brief review, we focus on the regulatory actions of LXR primarily in macrophages responding to a proatherogenic environment. LXR potentially interferes with atherosclerosis by 2 different agonist-dependent signaling pathways. The first is through promoting reverse cholesterol transportby directly activating genes of cellular cholesterol export. The second is through a general inhibitory action on proinflammatory genes where sumo-modified and agonist-bound LXR recruits negative coregulatory proteins to nuclear factor κB at immune response gene promoters through protein–protein interactions. The antiinflammatory actions of LXR may be a direct response to the proinflammatory actions recently proposed for cholesterol on inflammasome activity in the vessel wall.