Turbulent shear stresses created by the fluid dynamic characteristics of prosthetic valves cause damage to blood cells. Platelet activation and damage is extensively described and red blood cell hemolysis is reported in a significant number of valve replacements. Most of these studies have evaluated hemolysis in normal red cells and relate to different valves or replacement procedures rather than the red cell. Prehemolytic red cell damage is rarely considered and only few studies describe the effect of valve replacement on patients with red cell disorders. While hemolytic anemia is the ultimate end-point of valve-induced red cell damage, loss of red cells goes hand in hand with the formation of red cell-derived damaged membranes. It can be hypothesized that alterations (in subpopulations) of red cells and generation of red cell remnants due to the increased shear stress could have a profound physiologic effect before hemolytic anemia is apparent. In patients with red cell disorders, alterations in the red cell membrane suggest that red cell damage will be more pronounced after valve replacement. In this review, determinants of normal and abnormal red cell behavior under shear are discussed as well as some of the possible physiologic consequences of the formation of damaged red cell membranes.