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It is well known that hemostatic–thrombotic mechanisms are influenced by hemodynamic factors, such as shear forces affecting platelets or red blood cell aggregation, in turn affecting flow in stenotic regions. Endothelial cell function is also significantly influenced by shear forces acting on the vessel wall. Further, the distribution of shear forces in the vasculature is complex and closely associated with factors determining the flow properties of blood. Therefore, there is a link among alterations in the rheological properties of blood and its elements and the risk for thrombosis, with this linkage confirmed by numerous clinical studies. After discussing relevant rheological and hemodynamic concepts, this review focuses on selected drug-induced conditions that are known to be associated with both hyperviscosity conditions and increased thrombotic risk: oral contraceptives, diuretics, intravenous immunoglobulin, erythropoiesis-stimulating agents, chemotherapy, and radio-contrast media. Alterations of relationships between blood rheology and thrombotic risk related to artificial circulatory environments and physical exercise are also briefly discussed.