ABO blood group system discovery was an important step in development of such areas as transplantation and transfusion medicine. At the same time understanding of fundamental role of antigenic determinants in physiological functions maintenance and pathological conditions development remained unexplained for a long time. Today it is known that A and B antigens are widely represented not only on erythrocytes membrane but also on other cells and tissues: platelets, epithelial tissue, oral and spermal fluids. Earlier authors studied metabolic and coagulation profiles, as well as blood cells composition in clinically healthy individuals on more than 180,000 donations, thus revealing group-specific features for each blood group. The review provides synthesis of association of such pathological conditions as coronary heart disease, thromboembolic complications, tumors of various localizations, inflammatory and destructive oral diseases, psychiatric and some infectious diseases with the presence or absence of antigenic determinants A and B. 0 (I) blood group carriers are more resistant to development of diseases, excepting H. pylori-associated gastrointestinal diseases. Carriers of “antigenic” blood groups A (II), B (III), AB (IV) are more susceptible to infections, cardiovascular diseases, and oncological diseases. The data presented may contribute to a personalized patient approach formation, based on antigen-associated biological variability of various signs in norm and pathology.