Nanozymes represent a class of nanosized materials that exhibit innate catalytic properties similar to biological enzymes. The unique features of these materials have positioned them as promising candidates for applications in clinical sensing devices, specifically those employed at the point-of-care. They notably have found use as a means to amplify signals in nanosensor-based platforms and thereby improve sensor detection limits. Recent developments in the understanding of the fundamental chemistries underpinning these materials have enabled the development of highly effective nanozymes capable of sensing clinically relevant biomarkers at detection limits that compete with “gold-standard” techniques. However, there remain considerable hurdles that need to be overcome before these nanozyme-based sensors can be utilized in a platform ready for clinical use. An overview of the current understandings of nanozymes for disease diagnostics and biosensing applications and the unmet challenges that must be considered prior to their translation in clinical diagnostic tests is provided.