Biointerfaced sensors have emerged as a new paradigm for medical applications that require an interface and/or intimate contact with biological components/systems such as cells, tissues, and whole organs. This article provides a review of the concept, design, and device characteristics of biointerfaced sensors needed for successful implementation of biodiagnostics and monitoring. It begins by presenting and discussing the different considerations that arise from artificial interfaces with different biological environments. It then explores the main strategies for sensor and material design, while highlighting the required chemistry, structure, and mechanical properties needed to maintain an unperturbed interface with the surrounding biological environment. Finally, the review discusses successful state-of-the-art demonstrations of body monitoring and biodiagnostics, focusing on the brain, heart, muscles, skin, teeth, and other tissues for medical purposes. Insights, perspectives, and recommendations for future research are presented.