The growing power demands of wearable electronic devices have stimulated the development of on-body energy harvesting strategies. This article reviews the recent progress on rapidly emerging wearable biofuel cells (BFCs), along with related challenges and prospects. Advanced on-body BFCs in various wearable platforms, e.g., textiles, patches, temporary tattoo, or contact lenses, have enabled attractive advantages for bioenergy harnessing and self-powered biosensing. These noninvasive BFCs open up unique opportunities for utilizing bioenergy or monitoring biomarkers present in biofluids, e.g., sweat, saliva, interstitial fluid, and tears, toward new biomedical, fitness or defense applications. However, the realization of effective wearable BFC requires high-quality enzymeelectronic interface with efficient enzymatic and electrochemical processes and mechanical flexibility. Understanding the kinetics and mechanisms involved in the electron transfer process, as well as enzyme immobilization techniques, is essential for efficient and stable bioenergy harvesting under diverse mechanical strains and changing operational conditions expected in different biofluids and in a variety of outdoor activities. These key challenges of wearable BFCs are discussed along with potential solutions and future prospects. Understanding these obstacles and opportunities is crucial for transforming traditional bench-top BFCs to effective and successful wearable BFCs.