**1. Introduction**

Human red blood cells (RBCs) or erythrocytes have remarkable deformability. Upon external forces, RBCs undergo large mechanical deformation without rupture, and they restore to original shapes when released. The deformability of RBCs plays crucially important roles in the main function of RBCs - oxygen transport through blood circulation. RBCs must withstand large deformations during repeated passages through the microvasculature and the fenestrated walls of the splenic sinusoids (Waugh and Evans, 1979). RBC deformability can be significantly altered by various pathophysiological conditions, and the alterations in RBC deformability in turn influence pathophysiology, since RBC deformability is an important determinant of blood viscosity and thus blood circulation. Hence, measuring the deformability of RBCs holds the key to understanding RBC related diseases. For the past years, various experimental techniques have been developed to measure RBC deformability and recent technical advances revolutionize the way we study RBCs and their roles in hematology. This chapter reviews a variety of tools for measuring RBC deformability. For each technique, we seek to provide insights how these deformability measurement techniques can improve the study of RBC pathophysiology.
