Integrin-mediated cellular events affect all cell types and functions, in physiological as well as pathological settings. Blood platelets, because of their unique nature, have proven to be a powerful cell model with which to study the adhesive and signaling properties of integrins. The characterization of the structural and molecular mechanisms regulating the main platelet integrin, alphaIIbbeta3, has provided some essential clues as to how integrins are regulated in general. The present chapter details the various protocols and reagents currently in use in our laboratory to study alphaIIbbeta3 adhesive responses and signaling in both human and murine cell models.