Nuclear receptors are ligand-dependent transcription factors that recently have been shown to play important roles in the metabolism of cholesterol and bile acids. Cholesterol homeostasis is maintained by de novo synthesis, absorption from diet, catabolism to bile acids and other steroids, and excretion into bile. Dysregulation of this mechanism leads to atherosclerosis and its life-threatening coronary and cerebrovascular sequelae. Conversion of cholesterol to bile acids in the liver is positively regulated by liver X receptor (LXR) alpha, a nuclear receptor for oxysterols. LXRalpha and LXRbeta, a second oxysterol receptor, regulate intestinal absorption and biliary excretion of cholesterol by inducing target gene expression. LXRs stimulate reverse cholesterol transport from peripheral tissues and exhibit antiatherogenic activity. Farnesoid X receptor (FXR), a bile acid receptor, represses bile acid synthesis and import in hepatocytes, stimulates bile acid export from cells, and protects hepatocytes from bile acid toxicity. Pregnane X receptor (PXR) and vitamin D receptor (VDR) respond to secondary bile acids and induce their catabolism. Thus, nuclear receptors play important roles in regulation of cholesterol and bile acid metabolism.