The article discusses two studies on the activity of ephrin-B2, transmembrane ligand for EphB receptor tyrosine kinases. The authors cite the role of ephrin-B2 in signaling and control of the internalization of vascular endothelial growth factor (VEGF) receptors. The authors also elaborate how ephrin-B2 activates angiogenesis, tip cell filopodial extension, and lymphangiogenesis.