The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development. Multiple experimental, epidemiological, and clinical evidence underpins this association. Atherosclerotic cardiovascular disease remains as the major cause of mortality in the world. Recent genetic studies of Mendelian randomisation and randomised clinical trials aimed at LDL cholesterol reduction, are summarised in this article. They, unequivocally ratify the aetiological role of LDL cholesterol in the development of atherosclerosis. Thus, LDL cholesterol lowering is the cornerstone of lipid lowering therapy for the reduction of cardiovascular complications of atherosclerosis.