Macrophages play central roles in immunity and homeostasis, and contribute to the pathogenesis of atherosclerosis through their accumulation of cholesterol and the production of inflammatory mediators and cytokines. Recent studies indicate that oxysterols influence diverse aspects of macrophage biology. Rather than simply being intermediates of cholesterol catabolism, oxysterols are also potent bioactive lipids that regulate lipid metabolism, immune function, and cytotoxicity. These functions are mediated by specific oxysterol sensors, including liver X receptors (LXR), Insigs, and members of the oxysterol binding protein (OSBP) and OSBP-related protein family. The mechanisms of oxysterol-induced functions and their physiological roles in macrophages are reviewed. (Circ J 2010; 74: 2045-2051)