Oxidized derivatives of cholesterol have been investigated actively for decades in the context of the oxidative hypothesis of atherosclerosis. Oxysterols arise in our tissues as a result of enzymatic or non-enzymatic oxidation reactions and are also obtained from dietary sources. Even though these compounds are found enriched in the atherosclerotic lesions in arterial walls, the plasma concentrations of oxysterols cannot, in the light of current knowledge, be regarded as a risk factor for atherosclerotic disease. However, oxysterols may still have important local effects in the arterial wall as factors that regulate the cellular lipid homeostasis and possibly the maturation of the lesions. Work during the past few years has revealed that oxysterols have a potential as signaling molecules that may play important roles in lipid metabolism, especially the reverse cholesterol transport process. This finding has recently moved oxysterols and the protein mediators of their biological effects, liver X receptors and cytosolic oxysterol binding proteins, into the center stage of atherosclerosis research.