This piece offers perspectives on the emerging roles of lysophospholipids, which include lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), for the biology and pathophysiology of the nervous system. It reflects opinions generated during a meeting sponsored by the National Institute on Drug Abuse (NIDA) entitled "Targeted Lipidomics: Signaling Lipids and Drugs of Abuse" held in Washington, D.C., 15-17 April 2004, organized by Dr. Rao Rapaka. Lysophospholipids represent one class of lipids that has many important actions mediated by G protein-coupled receptors. While influencing a large number of biologically important systems, this discussion will focus on the nervous system, including areas of future research.