Olfactomedin-like 3 (Olfml3), a proangiogenic cue and a BMP4 agonist, is produced by both tumor endothelial cells and accompanying pericytes and deposited in the perivascular compartment. Blocking Olfml3 regresses the tumor vasculature, decreases pericyte coverage, and inhibits the progression of tumors. Olfml3 blockade provides an alternative strategy to control tumor growth by targeting a single molecule that affects two distinct cell types within the tumor microenvironment. For details, see article by Miljkovic-Licina and colleagues on page 2588.