Real-time “on-body” monitoring of human physiological signals through wearable systems developed on flexible substrates (e-skin) is the next target in human health control and prevention, while an alternative to bulky diagnostic devices routinely used in clinics. The present work summarizes the recent trends in the development of e-skin systems. Firstly, we revised the material development for e-skin systems. Secondly, aspects related to fabrication techniques were presented. Next, the main applications of e-skin systems in monitoring, such as temperature, pulse, and other bio-electric signals related to health status, were analyzed. Finally, aspects regarding the power supply and signal processing were discussed. The special features of e-skin as identified contribute clearly to the developing potential as in situ diagnostic tool for further implementation in clinical practice at patient personal levels.