The modulation of intracellular calcium ion concentration, Ca(2+), is a common signalling mechanism used in many biological systems. B and T lymphocytes rely on Ca(2+) signalling to initiate both developmental and activation programs. Recent data has shed new light on the initiation of this signalling pathway, the connection between the release of intracellular Ca(2+) stores and the influx of extracellular Ca(2+), and the molecular identity of the elusive Ca(2+) release-activated Ca(2+) (CRAC) channel. In addition, recent gene profiling of T lymphocytes has identified the genes that are controlled by Ca(2+) and the Ca(2+)-dependent phosphatase calcineurin.