This review takes stock of the various optical fiber-based biosensors that could be used for in vivo applications. We discuss the characteristics that biosensors must have to be suitable for such applications and the corresponding transduction modes. In particular, we focus on optical fiber biosensors based on fluorescence, evanescent wave, plasmonics, interferometry, and Raman phenomenon. The operational principles, implemented solutions, and performances are described and debated. The different sensing configurations, such as the side- and tip-based fiber biosensors, are illustrated, and their adaptation for in vivo measurements is discussed. The required implementation of multiplexed biosensing on optical fibers is shown. In particular, the use of multi-fiber assemblies, one of the most optimal configurations for multiplexed detection, is discussed. Different possibilities for multiple localized functionalizations on optical fibers are presented. A final section is devoted to the practical in vivo use of fiber-based biosensors, covering regulatory, sterilization, and packaging aspects. Finally, the trends and required improvements in this promising and emerging field are analyzed and discussed.