Recent developments in wearable and implanted devices have resulted in numerous, unprecedented capabilities that generate increasingly detailed information about a user's health or provide targeted therapy. However, options for powering such systems remain limited to conventional batteries which are large and have toxic components and as such are not suitable for close integration with the human body. This review provides an in‐depth overview of biofluid‐activated electrochemical energy devices, an emerging class of energy sources judiciously designed for biomedical applications. These unconventional energy devices are composed of biocompatible materials that harness the inherent chemistries of various biofluids to produce useable electrical energy. This article covers examples of such biofluid‐activated energy devices in the form of biofuel cells, batteries, and supercapacitors. Advances in materials, design engineering, and biotechnology that form the basis for high performance, biofluid‐activated energy devices are discussed. Innovations in hybrid manufacturing and heterogeneous integration of device components to maximize power output are also included. Finally, key challenges and future scope of this nascent field are provided.This article is protected by copyright. All rights reserved