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We review major experimental and theoretical studies on microcirculation and hemorheology, focusing on mechanics of blood flow and the vascular wall. We discuss flow of the blood formed elements [red blood cells (RBCs), white blood cells or leukocytes (WBCs) and platelets] in individual arterioles, capillaries, and venules, and in microvascular networks. We also review mechanical and rheological properties of the formed elements and their interactions with the vascular wall. We discuss short-term and long-term regulation of the microvasculature; the modes of regulation include metabolic, myogenic, and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.