The effective reduction of atherogenic lipoproteins has contributed to the rate of atherosclerosis-related cardiovascular complications being approximately halved over the last 50 years. Nevertheless, cardiovascular disease will be the leading cause of death worldwide in the coming years. The focus of this review is on the clinical significance of the pathophysiology of changes in lipid and lipoprotein metabolism. Elevated levels of atherogenic lipoproteins are a causal risk factor for atherosclerotic cardiovascular disease. Primary forms of hypercholesterolaemia have a significantly higher ASCVD risk because of the already lifelong LDL elevation (higher cumulative LDL exposure for the vessel wall). Secondary changes in lipid and lipoprotein metabolism (e. g. in diabetes or hypothyroidism) must be excluded or treated. Regulatory key steps in the pathophysiology of lipid metabolism and atherosclerotic plaque are "drug targets" for existing and new lipid and lipoprotein modifying therapies.