Changes in cellular Ca 2รพ concentrations form a ubiquitous signal regulating numerous processes such as fertilization, differentiation, proliferation, contraction, and secretion. The Ca 2รพ signal, highly organized in space and time, is generated by the cellular Ca 2รพ signaling toolkit. Lysophospholipids, such as sphingosine-1-phosphate (S1P), sphingosylphosphorylcholine (SPC), or lysophosphatidic acid (LPA) use this toolkit in a specific manner to initiate their cellular responses. Acting as agonists at G protein-coupled receptors, S1P, SPC, and LPA increase the intracellular free Ca 2รพ concentration ([Ca 2รพ ] i ) by using the classical, phospholipase C (PLC)-dependent pathway as well as PLCindependent pathways such as sphingosine kinase (SphK)/S1P. The S1P 1 receptor, via protein kinase C, inhibits the [Ca 2รพ ] i transients caused by other receptors. Both S1P and SPC also act intracellularly to regulate [Ca 2รพ ] i . Intracellular S1P mobilizes Ca 2รพ in intact cells independently of G protein-coupled S1P receptors, and Ca 2รพ signaling by many agonists requires SphK-mediated S1P production. As shown for the FceRI receptor, PLC and SphK may contribute specific components to the overall [Ca 2รพ ] i transient. Of the many open questions, identification of the intracellular S1P target site(s) appears to be of particular importance.