Muscle glycogen is an important fuel for contracting skeletal muscle during prolonged strenuous exercise, and glycogen depletion has been implicated in muscle fatigue. It is also apparent that glycogen availability can exert important effects on a range of metabolic and cellular processes. These processes include carbohydrate, fat and protein metabolism during exercise, post-exercise glycogen resynthesis, excitation–contraction coupling, insulin action and gene transcription. For example, low muscle glycogen is associated with reduced muscle glycogenolysis, increased glucose and NEFA uptake and protein degradation, accelerated glycogen resynthesis, impaired excitation–contraction coupling, enhanced insulin action and potentiation of the exercise-induced increases in transcription of metabolic genes. Future studies should identify the mechanisms underlying, and the functional importance of, the association between glycogen availability and these processes.