Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca2+ channels that are almost ubiquitously expressed in animal cells. The spatiotemporal complexity of the Ca2+ signals evoked by IP3R underlies their versatility in cellular signaling. Here we review the mechanisms that contribute to the subcellular targeting of IP3R and the dynamic interplay between IP3R that underpin their ability to generate complex intracellular Ca2+ signals.