Human erythrocytes express a relatively large number of known adhesion receptors, despite the fact that red blood cells (RBCs) are generally considered to be nonadhesive for endothelial cell surfaces. Some of these adhesion receptors are expressed by many other tissues, while others have more limited tissue distribution. Some adhesion receptors, including CD36 and VLA-4, are only expressed by immature erythroid cells, while others are present on mature erythrocytes. The structure and function of these proteins is reviewed here. LW, CD36, CD58, and CD147 have been shown in other tissues to mediate cell-cell interaction. Other receptors, such as CD44, VLA-4, and B-CAM/LU, can mediate adhesion to components of extracellular matrix. In addition, their roles in normal erythropolesis, as well as in the pathophysiology of human disease, are summarized. The most convincing evidence for a pathophysiologic role for any of these receptors on erythrocytes comes from studies of cells from patients homozygous for hemoglobin S, as RBC adhesion is thought to contribute to vaso-occlusion. Thus, receptors such as B-CAM/LU may become targets for future therapy aimed at preventing or ameliorating this thrombotic process.