Despite important advances in diagnostic medical techniques, feverof unknown origin (FUO) still remains a major challenge. This article tries to determine how much the 18F-fluorodeoxyglucose positron emission tomography coupled to computed tomography (FDG-PET/CT) contributes to the final diagnosis explaining FUO. It also analyzes whether its position in the investigation algorithm may be defined precisely. Our literature review revealed that FDG-PET/CT demonstrates an important potential to replace some traditional radiographic tests but that its position in the strategy of investigations remains to be further defined. The available studies are presently scarce, heterogeneous, and sometimes discordant.