Lactate (La−) is a ubiquitous carbohydrate-derived metabolite and a major player in the coordination of whole-body metabolism. As the redox-balanced end-product of glycolysis, La− forms the conceptual node linking glycolysis, a process that does not require oxygen, and which occurs in the cytosol, to the TCA cycle and aerobic bioenergetics in the mitochondria. Through rapid multisystem exchange involving membrane monocarboxylate transporters, lactate concentration ([La−]) in the blood offers a “snapshot” of relative rates of glycolytic La− production and its mitochondrial consumption. Thus, while strenuous physical activity elicits a transient La− accumulation, adaptations to exercise training often include attenuated [La−]s for a given submaximal work rate, as well as lower [La−]s at rest. Conversely, elevated resting [La−] in the fasted state can reflect an often-ortentous metabolic scenario involving multisystem metabolic (dys)function characteristic of acute and chronic health issues. At the cellular level, tumors often exhibit augmented glucose uptake and preferential production of La−, even in the presence of oxygen (i.e., the Warburg effect). From coordination of whole-body metabolism during exercise to signaling in cancer cells, the role of La− in metabolism continues to expand and holds potential for multiple clinical and sub-clinical applications.