This chapter summarizes the current knowledge and proposes a structural model for the function of elongation factor G (EF-G). The large number of mutations associated with fusidic acid resistance are an essential ingredient in this analysis. Recent investigations of a mutant EF-G with a different crystal packing have led to a complete interpretation of domain III at relatively low resolution. The functional cycle of EF-G can be described as a number of states both on and off the ribosome. The different states of EF-G may not necessarily be associated with different conformations of EF-G, but to the extent that there are different conformations, they will be related to different states. The density of EF-G could be identified with difference methods and compared to the crystallographic GDP conformation. The mutant G16V is fusidic acid sensitive compared to wt Thermus thermophilus EF-G, which is relatively resistant to the antibiotic. During one of the subsequent steps, EF-G adopts an open conformation like the one observed by cryo-EM. Since it overlaps the A-site tRNA, translocation must already have occurred, as is well known from studies of fusidic acid inhibition of protein synthesis. When EF-G has dissociated, it has the intermediate GDP conformation.