Exercise is a potent energetic stressor and a major counter measure against metabolic disease. Timing of energetic stressors over the day may specify close alignment between tissue clocks and promote coherent and efficient temporal gating of metabolic processes. My team have integrated emerging omics technologies to interrogate biorhythms and physiological responses to energetic stressors. This led to an atlas of exercise metabolism, in which we mapped global metabolite responses of multiple tissues after exercise. Thus, we have made the surprising discovery that the therapeutic response to exercise is time-dependent. In fact, we have also shown that timing of exercise or meals throughout the day affects metabolism in people with obesity or type 2 diabetes, but the mechanism(s) are unknown. My team is advancing the notion of “chrono-exercise”. We integrate omics approaches with physiological phenotyping and downstream mechanistic analyses, to optimize metabolism by timing energetic stressors to the peak times of metabolic rhythms to positively impact cardiometabolic health. In lecture, I will present emerging evidence that timing may optimize the adaptive response to exercise and improve health outcomes. Chrono-exercise may optimize metabolism by timing energetic stress during the day to improve insulin sensitivity and glycemia, and thereby positively impact metabolic health.