The Precision Medicine Initiative challenges biomedical researchers to reframe health optimization and disease treatment in a patient-specific, personalized manner. Rather than a one-size-fits-all paradigm, the charge is for a particular profile to be fit to each patient, and for disease treatment (or wellness) strategies to then be tailored accordingly. Non-invasive physiological sensing and modulation can play an important role in this effort by augmenting existing research in ‑omics and medical imaging towards better developing such personalized models for patients, and in continuously adjusting such models to optimize therapies in real-time to meet patients’ changing needs. While in many instances the focus of such efforts is on disease treatment, optimizing performance for healthy individuals is also a compelling need. This talk will focus on my group’s research on non-invasive sensing of the sounds and vibrations of the body, with application to musculoskeletal and cardiovascular monitoring applications. In the first half of the talk, I will discuss our studies that are elucidating mechanisms behind the sounds of the knees, and particularly the characteristics of such sounds that change with acute injuries. We use miniature microelectromechanical systems (MEMS) air-based and piezoelectric contact microphones to capture joint sounds emitted during movement, then apply data analytics techniques to both visualize and quantify differences between healthy and injured knees. In the second half of the talk, I will describe our work studying the vibrations of the body in response to the heartbeat using modified weighing scales and wearable MEMS accelerometers. Our group has extensively studied the timings of such vibrations in relation to the electrophysiology of the heart, and how such timings change for patients with cardiovascular diseases during treatment. Ultimately, we envision that these technologies can enable personalized titration of care and optimization of performance to reduce injuries and rehabilitation time for athletes and soldiers, improve the quality of life for patients with heart disease, and reduce overall healthcare costs.