Lysophosphatidic acid (LPA), its sphingolipid homolog sphingosine 1-phosphate (S1P) and several other related molecules constitute a family of bioactive lipid phosphoric acids that function as receptor-active mediators with roles in cell growth, differentiation, inflammation, immunomodulation, apoptosis and development. LPA and S1P are present in physiologically relevant concentrations in the circulation. In isolated cell culture systems or animal models, these lipids exert a range of effects that suggest that S1P and LPA could play important roles in maintaining normal vascular homeostasis and in vascular injury responses. LPA and S1P act on a series of G protein-coupled receptors, and LPA may also be an endogenous regulator of PPAR gamma activity. In this review, we discuss potential roles for lysolipid signaling in the vasculature and mechanisms by which these bioactive lipids could contribute to cardiovascular disease.