Ca 2+ is a highly versatile intracellular signal that operates over a wide temporal range to regulate many different cellular processes. An extensive Ca 2+-signalling toolkit is used to assemble signalling systems with very different spatial and temporal dynamics. Rapid highly localized Ca 2+ spikes regulate fast responses, whereas slower responses are controlled by repetitive global Ca 2+ transients or intracellular Ca 2+ waves. Ca 2+ has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease.