Major experimental and theoretical studies on microcirculation and hemorheology are reviewed with the focus on mechanics of blood flow and the vascular wall. 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 is discussed. Mechanical and rheological properties of the formed elements and their interactions with the vascular wall are reviewed. Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.