Robo4 (roundabout homolog 4 or magic roundabout) is a receptor for Slit proteins which implicate in angiogenesis and vascular patterning especially through facilitating inhibition of primary endothelial cell migration. It is a fairly recently identified member of Robo family and is shorter than other Robo members at both intracellular as well as extracellular domains. Robo4 plays important roles in several aspects of vascular development such as the guidance of endothelial cell migration, cell cycle regulation, inhibition of pathologic angiogenesis and endothelial hyperpermeability etc. Employing mouse and zebrafish models, Slit2/Robo4 interactions have been shown to maintain integrity of vascular network and its barrier function by inhibiting cytokine-mediated vasculogenesis with enhanced permeability, and that Slit2-Robo4-paxillin-GIT1 network inhibits neovascularization and vascular leakage. Moreover, single nucleotide polymorphorism of Robo4 has been documented to be associated with autism suggesting its role in development and function of human brain.