Atherosclerotic diseases are the leading cause of mortality in industrialized countries. Correspondingly, studying the pathogenesis of atherosclerosis and developing new methods of its diagnostic and treatment remain in the focus of current medicine and health care. This review aims to discuss the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis. In particular, the generally accepted hypothesis about the key role of oxidized LDL in atherogenesis is questioned, and an alternative concept of multiple modification of LDL is presented. The fundamental question discussed in this review is whether LDL and HDL are effectors or biomarkers, or both. This is important for understanding whether lipoproteins are a therapeutic target or just diagnostic indicators.