Sweat is a largely unexplored biofluid that contains many important biomarkers ranging from electrolytes and metabolites to proteins, cytokines, antigens, and exogenous drugs. The eccrine and apocrine glands produce and excrete sweat through microscale pores on the epidermal surface, offering a noninvasive means for capturing and probing biomarkers that reflect hydration state, fatigue, nutrition, and physiological changes. Recent advances in skin-interfaced wearable sensors capable of real-time in situ sweat collection and analytics provide capabilities for continuous biochemical monitoring in an ambulatory mode of operation. This review presents a broad overview of sweat-based biochemical sensor technologies with an emphasis on enabling materials, designs, and target analytes of interest. The article concludes with a summary of challenges and opportunities for researchers and clinicians in this swiftly growing field.