Membrane protein topology is the starting point for predicting the threedimensional structure. Many membrane protein topologies have been determined by using several experimental approaches such as chemical modification and fusion-protein approach. Studied on membrane translocation and insertion have determined two possible inserting structural elements.Statistical studies on membrane proteins with known topology and engineering membrane protein topology indicate a universal positive inside rule of helical-bundle proteins. Reliable strategies have been developed to predict the topology of membrane proteins, which is of great importance to reverse biology. But there is still a long way to go to make three-dimensional structure predictions.