Previous articles in this series have emphasized the fundamental importance of adhesion receptors in vascular biology. One class of these receptors, the integrins, is necessary for vascular and hematopoietic cell development, angiogenesis, cell migration in response to injury, and extracellular matrix assembly. Furthermore, an integrin specific to platelets and megakaryocytes, ɑIIbß3, is indispensable for hemostasis and has become a validated therapeutic target for antithrombotic drugs. Thus, these widely distributed receptors play prominent roles in normal vascular biology and pathology. Integrins are noncovalent ɑß heterodimers. Each subunit consists of a relatively large NH2-terminal extracellular domain, a single membrane-spanning domain, and a COOH-terminal cytoplasmic tail. So far, at least 17 different integrin ɑ subunits and 8 ß subunits have been cloned and over 20 different ɑß pairings have been identified in vertebrate tissues. Integrins were originally identified because of their adhesive properties. Now, multiple lines of evidence indicate that they also function as signaling receptors and that integrin signaling is as vital to vascular cells as is integrin adhesion. The term integrin signaling refers to the capacity of these receptors to transmit information in both directions across the plasma membrane. There has been a recent convergence of scientific interest at this interface of cell adhesion and signaling, and several pertinent reviews are available (1–8). Our purpose here is to outline what is encompassed by the concept of integrin signaling and to present several emerging principles concerning its mechanisms.