Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that transmits signals through a family of G-protein-coupled receptors to control cellular differentiation and survival, as well as the vital functions of several types of immune cell. In this Review article, we discuss recent results that indicate that S1P and its receptors are required for the emigration of thymocytes from the thymus, the trafficking of lymphocytes in secondary lymphoid organs and the migration of B cells into splenic follicles. In an autocrine manner, through interactions with different G-protein-coupled receptors, S1P also enhances optimal mast-cell migration and release of pro-inflammatory mediators in allergic reactions. S1P-S1P-receptor regulatory systems might therefore be novel targets for the therapy of diverse immunological diseases.