Calcium is a pleiotropic messenger controlling a diverse array of intracellular events from fertilization to cell death. One of the main mechanisms by which intracellular calcium is elevated is through InsP(3) [Ins(1,4,5)P(3)]-induced mobilization of calcium from its receptor on the endoplasmic reticulum calcium store. The activity of the InsP(3)R (InsP(3) receptor) is subject to regulation by many factors other than InsP(3), most notably calcium itself, which regulates the channel in a bell-shaped dependent manner. InsP(3)R sensitivity is also regulated by post-translational modifications such as phosphorylation and by binding of accessory proteins. Taken together it appears that the InsP(3)R can be regarded as a cellular sensor for many signalling pathways, qualitatively and quantitatively regulating intracellular calcium signals with consequences for downstream cellular physiology.