The evaluation of the clinical effectiveness of hemorheological treatment is particularly difficult due to the existence of several physiopathological and technical problems which, up to now, have not been solved. Blood rheological behavior depends on plasma and cellular determinants, and regarding the latter the red cells play a major role. Some hyperviscosity clinical patterns related either to qualitative and quantitative alterations of plasma proteins or to an increase in red blood cells are now treated using mechanical removal techniques, while the pharmacological treatment is disappointing. The anatomo-functional red cell trend can be modified by membrane alterations, by alterations of the cytoplasmatic metabolic systems and by extra-erythrocyte factors. The rheological role of the anatomo-functional integrity of the membrane and the red cell content of Ca2+ and ATP have been evidentiated; the extra-erythrocyte factors are now being carefully studied. At present, a demonstration of the rheological activity and clinical effectiveness of drugs able to modify the erythrocyte levels of Ca2+ and ATP is evident. The pharmacological approach, acting on membrane phospholipids, about which there are several reports, is interesting and also the group of drugs influencing prostaglandin system and platelet aggregation is important. We have only incomplete reports regarding several other drugs. The future of the therapeutic use of drugs acting on blood rheology is interesting, but a final answer will derive only by examining their clinical effectiveness.