The contribution of high serum levels of cholesterol to atherogenesis has been widely recognized, but the mechanisms are not completely clear. Numerous publications have emphasized that oxidized, but not native low-density lipoproteins, are the particles incorporated into the arterial wall. A group of receptors generically called "scavenger" (SR), actively bind these modified lipoproteins and incorporate them into monocytes-macrophages, in the arterial intima. SR are not down regulated by intracellular concentrations of cholesterol, thus accumulating huge amounts of lipids, transforming monocyte-macrophages into foam cells, predominant cell type of the fatty streak. The simultaneous cytokine production and migration of other cellular types progressively transform this initial lesion into the organized atherosclerotic plaque. In this setting SR, which are up-regulated by oxidized LDL, play a central promoting role. Its presence has been demonstrated in arterial plaques both in human and animal models, and its blockade protects animals from development or progression of atherosclerosis. In humans, elevated antibody titers to oxidized LDL in patients with coronary stenosis, and increased SR activity, in pro-atherogenic conditions such as haemodyalisis, indicate that this model may operate as well, but the evidences are still not solid enough to definitively conclude that the oxidized-LDL-SR hypothesis is a finished puzzle.