Ultrathin wearable sensors have emerged as a transformative platform for next-generation health and performance monitoring, offering intimate integration with human skin for real-time physiological and biochemical sensing based upon electrophysical and electrochemical response at human-sensor interfaces. These sensory systems, often composed of micrometer-to-nanometer-thick functional responsive materials, achieve seamless integration at skin-electronics interfaces by mimicking the dynamic and mechanical properties of human skin. Recent advances in material synthesis, nanoscale engineering, and structural design have enabled novel sensors that are not only stretchable and breathable but also robust, biocompatible, and highly responsive. This review highlights the fundamental materials principles governing skin-conformal interactions, explores various material systems, including planar, porous, and hybrid architectures, and outlines state-of-the-art developments in smart adhesives, wearable ultrathin sensors, responsive behavior, true conformability, and printed sensors. We discuss the broad spectrum of current and prospective applications, from tactile and electrophysiological sensing to biochemical and multimodal wearable devices, as well as key challenges, existing trends, and future prospects.