The role of integrin receptors in regulating numerous cellular programs have been well studied in the endocrine pancreas. These adhesion receptors and their interactions with the extracellular matrix (ECM) are important determinants of islet cell biology as they influence the development, survival and function of the islets of Langerhans. In this review, we will discuss the profound role of integrin-ECM relationships in controlling pancreatic tissue morphogenesis and the anti-apoptotic properties that these receptors confer through their dynamic and unique signaling pathways. Relationships between the ECM-integrin receptors will also be discussed in light of islet-based therapies including transplantation procedures and pancreatic tissue engineering initiatives.