The ABO blood group system was discovered one hundred years ago; the respective ABH antigens were found in the protein and lipid membrane components of various cells (most importantly, erythrocytes) and soluble blood group substances. The genetics of the ABO system was also elucidated. This old knowledge is still useful, bringing new applications. Although we do not really know the complete biological role of blood group systems, including that of the major ABO system, data, which is still being accumulated, ensure scientists and physicians of its imoprtance in research and the diagnosis and therapy of diseases. For example, susceptibility to some diseases has been shown to be connected with the blood group of the patient, or the phenotype changes of the ABH determinants may indicate the presence of defined form of cancer. The data presented in this article clearly suggest the validity of the ABO blood group system in medical and biological sciences.