Photonic technologies have made enormous impacts on modern medicine, advancing disease diagnostics and treatments as well as health monitoring. A long-standing challenge in the use of light and its widespread effects in photomedicine is the finite penetration of light in tissues. However, judiciously engineered optical fibers helped overcome this challenge and advance light delivery to deep tissues with spatial precision and desired accessibility. In recent years, the development of photonic technologies including optical biomaterials, fiber functionalization, and biomedical device innovations has greatly expanded the scope of light-based healthcare. Here, the fundamentals and materials of fiber optics to endow themselves with biocompatibility, flexibility, and diverse functionalities required for long-term implantation are overviewed. The design strategies of lab-on-fiber techniques, operation requirements to construct fiber optic sensors, and their health monitoring applications as wearable and implantable devices are presented. The use of fiber optics in major light-based therapeutic modalities including optogenetics, photodynamic therapy, photobiomodulation, photochemical cross–linking, and photothermal therapy is illustrated to enhance their effectiveness, specificity, and feasibility. In short, a comprehensive review is provided on the fiber optic techniques and the latest photonic devices, which are envisioned to evolve photomedicine in clinical and point-of-care practices.