Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that has been shown to regulate cell growth, cell survival, cell invasion, vascular maturation, and angiogenesis, processes that are important for cancer progression. In this issue of Cancer Cell, Visentin et al. demonstrate that a monoclonal antibody that binds S1P with extremely high affinity and specificity significantly slows tumor progression and associated angiogenesis in several animal models of human cancer. Their results suggest that S1P not only affects tumor cells themselves, but also is permissive or required for the actions of angiogenic factors, and thus may be a bona fide cancer target.