Qi Lu, Y. Wu, Tanja Weil
ABSTRACT Free radicals play central roles in cellular signaling and disease, yet their short lifetimes, low steady‐state concentrations, and pronounced spatial heterogeneity make them notoriously difficult to detect in living systems. Conventional approaches, including luminescent probes and electron spin resonance (ESR) spectroscopy, have provided valuable insights but remain fundamentally limited by chemical perturbation, indirect readouts, ensemble averaging, or insufficient spatial resolution. Nanodiamonds (NDs) containing nitrogen‐vacancy (NV) centers offer a fundamentally different, quantum‐based sensing strategy. By exploiting T 1 relaxometry, NV centers directly detect changes in local magnetic noise associated with unpaired electrons, enabling label‐free and nondestructive measurements in close proximity to radical‐generating environments under physiological conditions. While T 1 relaxometry does not directly identify individual radical species, it provides spatially localized readouts of the local paramagnetic environment and thereby complements established radical detection methods. Owing to their exceptional photostability, chemical inertness, and biocompatibility, NDs are uniquely suited for longitudinal measurements at the single‐cell and subcellular level. This review places ND quantum sensing within the broader landscape of radical detection technologies, systematically comparing conventional methods and highlighting how their limitations motivate the use of NV‐based sensors. We discuss recent advances in ND‐enabled radical sensing in living systems, address key challenges including measurement artefacts, ND heterogeneity, surface‐ and environment‐dependent signal modulation, and the limited chemical specificity of T 1 ‐based readouts, and outline future opportunities in complex biological models. Together, these developments position NDs as a powerful and promising functional materials platform for probing redox‐active microenvironments and free radical biology in living systems.