Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (SIP) are the biologically predominant members of a family of mediators termed lysophos-pholipid growth factors (PLGFs) or lysophospho-lipids (LPLs). These amphipathic phospholipids are generated by platelets, macrophages, other leukocytes, epithelial cells, and some tumors in amounts that result in micromolar concentrations in serum and some tissue fluids. A family of G protein-coupled receptors bind LPA and SIP to transduce signals stimulating cellular proliferation, differentiation, survival, and cellular functions. LPA and SIP have roles in hemostasis, cardiovascular regulation, wound healing, cytoprotection, immunity, inflammation, and organ system development normally, and in the pathogenesis of some types of cancer.