Wearable sensor technologies play a significant role in realizing personalized medicine through continuously monitoring an individual’s health state. To this end, human sweat is an excellent candidate for non-invasive monitoring as it contains physiologically rich information. In this talk, I will present our recent advancements on fully-integrated perspiration analysis system that can simultaneously measure sweat rate, metabolites, electrolytes, drugs and heavy metals, as well as the skin temperature to calibrate the sensors’ response. Our work bridges the technological gap in wearable biosensors by merging plastic-based sensors that interface with the skin, and silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This wearable system is used to measure the detailed sweat profile of subjects engaged in prolonged physical activities, and infer real-time assessment of physiological state of the subjects. Case studies on the correlation of sweat analytes with those of blood and various physiological conditions will be presented, including for applications in dehydration studies, diabetes monitoring, drug metabolism rate studies, and detection and monitoring of cystic fibrosis. Finally, a general roadmap for the technology will be presented, with focus on opportunities and challenges.