The Robo (Roundabout) family of receptors is known for its guidance role during development. Studies have shown that one of the family members, Robo4, is specifically expressed in the vascular endothelium and may provide directional cues to migrating endothelial cells. Recent evidence shows that Robo4-deficient mice have increased angiogenesis, suggesting that Robo4 may play a role in restricting vascular sprouting.