Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data. Then, based on the state of the art, we describe sensing strategies that could be applied for the continuous monitoring of acute inflammatory biomarkers, followed by challenges that must be overcome. Nanoswitch-based continuous biosensors enable suitable measurement frequencies but still lack sensitivity, while regeneration risks lower sensor reliability. Developments are still needed in bioreceptors and molecular architectures, regeneration techniques, combined with suitable sampling and sample pretreatment methods, for bringing continuous biosensing of inflammation closer to reality. Furthermore, collaborations between healthcare professionals and scientists, regulatory bodies, and biosensor engineers are needed for a successful translation of sensing technologies from the laboratory to clinical practice.