**Abstract**

Integrating enzymes with wearable electrochemical systems delivers extraordinary functional devices, including biosensors and biofuel cells (BFCs). Strategies employing enzyme-based bioelectronics represent a unique foundation of wearables because of specific enzyme recognition and catalytic activities. Therefore, such electrochemical biodevices on various platforms, e.g., tattoos, textiles, and wearable accessories, are interesting. However, these devices need effective power sources, requiring combining effective energy sources, such as BFCs, onto compact and conformal platforms. Advantageously, bioenergy-harvesting BFCs can also act as self-powered sensors, simplifying wearable systems. Challenges pertaining to energy requirements and the integration of biocatalysts with electrodes should be considered. In this chapter, we detail updated advancement in skin-worn devices, including biosensors, BFCs, and self-powered sensors, along with engineering designs and on-skin iontophoretic strategies to extract biofluids. Crucial parameters including mechanical/material aspects (e.g., stretchability), electrochemistry, enzyme-related views (e.g., electron shuttles, immobilization, and behaviors), and oxygen dependency will be discussed, along with outlooks. Understanding such challenges and opportunities is important to revolutionize wearable devices for diverse applications.

**Keywords:** wearable technology, electrochemical devices, enzyme-based bioelectronics, biosensors, biofuel cells, self-powered biosensors, sweat, iontophoresis, personalized healthcare
