The discovery that lysophosphatidic acid (LPA) acts as a signaling molecule via its G protein-coupled receptors motivated studies on the signaling and pathophysiology of LPA. Furthermore, the subsequent identification of the LPA-producing plasma phosphodiesterase, autotaxin, led to structural and mouse genetic studies of this lysophospholipase D. Recently, translational studies using LPA receptor-deficient or autotaxin-deficient mice, as well as receptor specific antagonists and autotaxin inhibitors, have been reported. These reports suggest that autotaxin and LPA receptors are potential drug targets, and have attracted the attention of researchers involved in drug discovery in a variety of pathologies including cancer, fibrosis, inflammation, pain and cardiovascular diseases. In this review, the state of the art regarding translational research and the status of drug discovery efforts targeting LPA synthesis (autotaxin) and LPA signaling (LPA receptors) are discussed with an emphasis on potential clinica...