A microvascular network is a system of conduits that distributes blood throughout tissues. Flow of blood is driven by arterial pressure. Blood is a concentrated suspension of red blood cells (RBCs), and its apparent viscosity changes depending on hematocrit, tube diameter, and flow rate. Red blood cells do not divide in proportion to flow in diverging bifurcations, leading to wide variations in microvascular hematocrits. Microvessels are lined by a relatively thick endothelial surface layer (ESL) that substantially increases resistance to blood flow and affects the interaction of blood cells with the vessel wall. The stochastic nature of growth and remodeling of microvascular networks leads to substantial heterogeneity in their topological and morphological structures. To achieve adequate transport functions, including oxygen delivery to tissues, this heterogeneity must be compensated for by active biological processes that control network and vessel geometry, including structural adaptation and control of vascular tone. In the resulting network structures, most parameters describing microvessel geometry and flow show wide dispersions and significant correlations. Consequently, estimation of system functions based on average or typical parameter values may result in incorrect or misleading conclusions. Understanding these phenomena requires analysis of their consequences at the network level. The study of blood flow in microvascular networks represents a key step in the process of translating advances in molecular and cellular biology into improved understanding of cardiovascular function in health and disease.