<p>Continuous monitoring of chronic diseases with mobile health tools is rapidly advancing to improve patient care. Wearable sensors placed on or near the skin remain the dominant paradigm for collecting physiological data noninvasively during activities of daily living. However, wearable sensors have their limitations. Epidermal sensors are fundamentally limited by the information barrier that the skin presents. Furthermore, environmental factors impact the stability and longevity of wearables. An alternative technology is the expanding class of minimally invasive subdermal sensors, also called insertables. Key applications for subdermal sensors are reviewed, including three current clinical devices: insertable cardiac monitors, insertable continuous glucose monitors, and sub-scalp epilepsy monitors. Next, common challenges impacting performance are discussed, including device migration, device encapsulation, and misalignment with wirelessly linked wearables. Finally, recent technological advancements to mitigate these challenges are covered. With state-of-the-art approaches for achieving biocompatibility, remote powering, and wireless data transmission, the next generation of subdermal biosensors can be developed for unmet needs in chronic disease monitoring.</p>