The lysophospholipid mediators, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), are responsible for cell signaling in diverse pathways including survival, proliferation, motility, and differentiation. Most of this signaling occurs through an eight-member family of G-protein coupled receptors once known as the endothelial differentiation gene (EDG) family. More recently, the EDG receptors have been divided into two subfamilies: the lysophosphatidic acid subfamily, which includes LPA1, (EDG-2/VZG-1), LPA2 (EDG-4), and LPA3 (EDG-7), and the sphingosine-1-phosphate receptor subfamily, which includes S1P1 (EDG-1), S1P2 (EDG-5/H218/AGR16), S1P3 (EDG-3), S1P4 (EDG-6), and S1P5 (EDG-8/NRG-1). The ubiquitous expression of these receptors across species, coupled with their diverse cellular functions, has made lysophospholipid receptors an important focus of signal transduction research. Neuroscientists have recently begun to explore the role of lysophospholipid receptors in a number of cell types; this research has implicated these receptors in the survival, migration, and differentiation of cells in the mammalian nervous system.