Wearable biosensors are envisioned to disrupt both delivery and accessibility of healthcare by providing real-time, continuous monitoring of informative and predictive physiological markers in convenient, user-friendly, and portable designs. In recent years, there has been myriad demonstrations of biosensor-integrated clothing and skin-borne biosensor patches, enabled by device miniaturization, reduced power consumption, and new biosensing chemistries. Despite these impressive demonstrations, most consumer-grade wearables have been limited to biophotonic and biopotential sensing methods to extrapolate information such as pulse, blood oxygenation, and electrocardiograms. The only commercial example of wearable electrochemical sensing methods is for glucose monitoring. However, there is a growing interest in developing percutaneous biosensors for monitoring in interstitial fluid (ISF), which offers direct access to popular analytes such as glucose, lactate, and urea, as well as new targets like hormones, antibodies, and even medications. Herein, a brief context for the current status of wearable biosensors is provided and assess the major engineering successes and pitfalls of percutaneous biosensors over the past five years, with a view to identifying areas for further developments that will enable deployable, clinical- or consumer-grade systems. Following the commercial and technical success of continuous glucose monitors, there is accelerating interest in percutaneous biosensors for direct biomarker monitoring in the dermal interstitium. This review provides a survey and assesses the key successes and challenges met in the development of percutaneous biosensors over the past five years. It is aimed to highlight opportunities for further advancement to facilitate the deployment of clinical and consumer-grade systems. image