Slit-Robo regulates many physiologic processes, such as neuronal development, angiogenesis, organ development, cell proliferation, tumor and inflammatory response, and different downstream signal pathways can produce different physiological functions. Moreover, the interaction between Slit and Robo is not one-to-one, many Slit receptors other than Robo have been found, and Robo can also interact with ligands other than Slit. These interactions play a key role in the regulation of cell movement. This article reviews the current research progress of Slit-Robo signal transduction pathways, including the protein structure, proteolytic processing and physiological processes in vivo such as neural development, angiogenesis, organ development, cell proliferation, tumor and inflammatory response. However, the physiological processes of Slit-Robo are highly diverse, and how these differences are regulated remains unknown. We thus expect more basic and translational research.