Over the last three decades, much progress has been made in understanding the mechanisms and regulation of the cholesterol supply pathways that cells and tissues use to sate their demands for this essential membrane component. But how does the body get rid of excess cholesterol and by what means is the catabolic process regulated? These questions are of medical as well as scientific importance because controlled elimination is one of the body’s chief defenses against cholesterol accumulation and consequent heart attacks. Several recent papers address the essence of these questions and reveal potential physiological roles for three nuclear orphan receptors, the LXRα (or more properly NR1H2;