Ample evidence indicates that sphingosine-1-phosphate (SPP) can serve as an intracellular second messenger regulating calcium mobilization, and cell growth and survival. Moreover, the dynamic balance between levels of the sphingolipids metabolites, ceramide and SPP, and consequent regulation of opposing signaling pathways, is an important factor that determines whether a cell survives or dies. SPP has also recently been shown to be the ligand for the EDG-1 family of G protein-coupled receptors, which now includes EDG-1, -3, -5, -6, and -8. SPP is thus a lipid mediator that has novel dual actions signaling inside and outside of the cell. This review is focussed on sphingosine kinase, the enzyme that regulates levels of SPP and thus plays a critical role in diverse biological processes.