Aberrant wound healing responses to lung injury are believed to contribute to fibrotic lung diseases, such as idiopathic pulmonary fibrosis (IPF). The lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), by virtue of their ability to mediate many basic cellular functions, including survival, proliferation, migration, and contraction, can influence many of the biological processes involved in wound healing. Accordingly, recent investigations indicate that LPA and S1P may play critical roles in regulating the development of lung fibrosis. Here we review the evidence indicating that LPA and S1P regulate pulmonary fibrosis and the potential mechanisms through which these lysophospholipids may influence fibrogenesis induced by lung injury.