Current concepts of brain perfusion focus on the importance of rheological factors in the determination of cerebral blood flow. Blood viscosity, a primary determinant of blood flow, increases as the shear rate (velocity gradient) decreases, thereby impeding cerebral perfusion. Hematocrit, erythrocyte aggregation, erythrocyte flexibility, platelet aggregation, and plasma viscosity differentially influence blood flow through the conductance vessels and microcirculation of the brain. In addition, the microcirculation is also affected by the Fahraeus effect, the inversion phenomenon, and the screening effect. Knowledge of these factors affecting blood flow provides a rationale for experimental and clinical rheological therapies in the treatment or prevention of acute focal cerebral ischemia.