Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent phospholipid mediators with diverse biological activities. Their appearance and functional properties suggest possible roles in development, wound healing, and tissue regeneration. The growth-stimulating and other complex biological activities of LPA and S1P are attributable in part to the activation of multiple G protein-mediated intracellular signaling pathways. Several heterotrimeric G proteins, as well as Ras- and Rho-dependent pathways play central roles in the cellular responses to LPA and S1P. Recently, several G protein-coupled receptors encoded by a family of endothelial differentiation genes (edg) have been shown to bind LPA or S1P and transduce responses of cAMP, Ca2+, MAP kinases, Rho, and gene transcription. This review summarizes our current understanding of signaling pathways critical for cellular responses to LPA and S1P and of recent progress in the molecular biological analyses of the Edg receptors.