Netrin-1 is an axon guidance cue and is necessary for neural and vascular development. It is involved in regulating axon guidance for attraction or repulsion, and it has a dual function in endothelial tip cell migration during angiogenesis. Netrin-1 has been shown to play an important role in angiogenesis, cancer progression, and inflammatory disease. Here we review the role of netrin-1 in retinal and angiogenesis development and the associated signaling pathways in diabetic retinopathy. The currently available data suggest that netrin-1 is a promising target for the development of anti-angiogenesis drugs.