This invention provides for polypeptides that have surprising anti-angiogenic activity. These peptides are derived from Saposin B, a previously known protein involved in the hydrolysis of sphingolipids. In addition, methods of treating mammals with these anti-angiogenic polypeptides are provided, as well as the pharmaceutical compositions used to treat. Furthermore, the polypeptides of this invention can be used in fusion proteins, wherein the fusion proteins also comprise cell targeting or cytotoxic moieties. Also provided is the receptor to which these polypeptides bind.