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Examples span intracranial hypertension from traumatic brain injuries, high blood pressure from poor diet, pressure\u2010induced skin ulcers from immobility, and edema from congestive heart failure. Pressures measured on the soft surfaces of vital organs or within internal cavities of the body can provide essential insights into patient status and progression. Challenges lie in the development of high\u2010performance pressure sensors that can softly interface with biological tissues to enable safe monitoring for extended periods of time. This review focuses on recent advances in mechanically active materials and structural designs for classes of soft pressure sensors that have proven uses in these contexts. The discussions include applications of such sensors as implantable and wearable systems, with various unique capabilities in wireless continuous monitoring, minimally invasive deployment, natural degradation in biofluids, and\/or multiplexed spatiotemporal mapping. 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