Changes in cellular Ca²⁺ concentrations form a ubiquitous signal regulating numerous processes such as fertilization, differentiation, proliferation, contraction, and secretion. The Ca²⁺ signal, highly organized in space and time, is generated by the cellular Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]_i) by using the classical, phospholipase C (PLC)‐dependent pathway as well as PLC‐independent pathways such as sphingosine kinase (SphK)/S1P. The S1P₁ receptor, via protein kinase C, inhibits the [Ca²⁺]_i transients caused by other receptors. Both S1P and SPC also act intracellularly to regulate [Ca²⁺]_i. Intracellular S1P mobilizes Ca²⁺ in intact cells independently of G protein‐coupled S1P receptors, and Ca²⁺ signaling by many agonists requires SphK‐mediated S1P production. As shown for the FcεRI receptor, PLC and SphK may contribute specific components to the overall [Ca²⁺]_i transient. Of the many open questions, identification of the intracellular S1P target site(s) appears to be of particular importance.