Exercise is a powerful means to maintain health, prevent disease, and even act as medicine for a wide range of non-communicable diseases. The key effects by which exercise benefits our metabolic health include (i) events that occur during exercise and in the hours to days following exercise, and (ii) the adaptations that occur following long-term repeated exercise training. Here, we provide a contemporary overview of recent significant advances in our knowledge of exercise as medicine in metabolic disease with a focus on muscle glucose metabolism.