Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are expressed in nearly all animal cells, where they mediate the release of Ca(2+) from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca(2+) signals allows selective regulation of diverse physiological responses. Interactions of IP3 Rs with other proteins contribute to the specificity and speed of Ca(2+) signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3 Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3 Rs, facilitate their regulation by multiple signalling pathways and direct the Ca(2+) that they release to specific targets. We suggest that IP3 Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca(2+) signals.