Sweat is an important biofluid presents in the body since it regulates the internal body temperature, and it is relatively easy to access on the skin unlike other biofluids and contains several biomarkers that are also present in the blood. Although sweat sensing devices have recently displayed tremendous progress, most of the emerging devices primarily focus on the sensor development, integration with electronics, wearability, and data from in vitro studies and short-term on-body trials during exercise. To further the advances in sweat sensing technology, this review aims to present a comprehensive report on the approaches to access and manage sweat from the skin toward improved sweat collection and sensing. It is begun by delineating the sweat secretion mechanism through the skin, and the historical perspective of sweat, followed by a detailed discussion on the mechanisms governing sweat generation and management on the skin. It is concluded by presenting the advanced applications of sweat sensing, supported by a discussion of robust, extended-operation epidermal wearable devices aiming to strengthen personalized healthcare monitoring systems.