It is a pleasure to provide a commentary on the outstanding review1 by Dr. George Brooks that discusses both the discovery and importance of the lactate shuttle. Clearly, Professor Brooks is highly qualified to review this important topic. Indeed, Dr. Brooks and his colleagues pioneered the original research that defined the metabolic conditions that regulate lactate production in skeletal muscle as well as the fate of lactate following produc-tion. In the following paragraphs, I highlight several key con-cepts emerging from this important review.