There are now numerous emerging flexible and wearable sensing technologies that can perform a myriad of physical and physiological measurements. Rapid advances in developing and implementing such sensors in the last several years have demonstrated the growing significance and potential utility of this unique class of sensing platforms. Applications include wearable consumer electronics, soft robotics, medical prosthetics, electronic skin, and health monitoring. In this review, we provide a state-of-the-art overview of the emerging flexible and wearable sensing platforms for healthcare and biomedical applications. We first introduce the selection of flexible and stretchable materials and the fabrication of sensors based on these materials. We then compare the different solid-state and liquid-state physical sensing platforms and examine the mechanical deformation-based working mechanisms of these sensors. We also highlight some of the exciting applications of flexible and wearable physical sensors in emerging healthcare and biomedical applications, in particular for artificial electronic skins, physiological health monitoring and assessment, and therapeutic and drug delivery. Finally, we conclude this review by offering some insight into the challenges and opportunities facing this field.