The secretin receptor is a class B1 GPCR that has been demonstrated to associate with itself, with structurally-related receptors, and even with select receptors from another class of GPCRs. The predominant complex formed with itself represents a symmetrical homo-dimer, along the lipid face of transmembrane segment four. This exists constitutively, arriving at the plasma membrane in this form after biosynthesis and being unaffected by agonist binding. There is evidence to suggest that this state of the receptor is functionally important, contributing to its high affinity binding of natural agonist and the high potency of responses to secretin. It also explains the negative cooperativity responsible for the reduced affinity binding and biological activity of agonist occupation of the second protomer comprising this complex. These themes appear to be consistent among other family members, and most members of the class B GPCR family can not only form homo-dimers, but also associate with each other to form hetero-complexes. Such complexes can explain agonist-induced cross-internalization of the associated receptors, providing an important mechanism for receptor regulation. It will be important to explore the physiologic implications of these processes, and to examine whether they are important in vivo.