Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the 'response-to-retention' model - namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall.