Exercise results in a large and immediate increase in muscle energy demand that requires a coordinated integration of muscle fuel utilisation, which in non-pathological states is usually dictated by the availability of fuel substrate and the magnitude of increase in the energy demand of exercise. This lecture will focus on the regulation of muscle fuel utilisation in the rest to steady-state exercise transition period and during steady-state exercise. Furthermore, given that the pattern of muscle fuel use during exercise will influence fuel selection during recovery from exercise, this lecture will also hopefully set the scene for lectures to follow focused on the post-exercise recovery period. Specifically, this lecture will focus on the integration of oxygen dependent (mitochondrial) and oxygen independent (cytosolic) energy production during the non-steady state period at the onset of exercise, and the rate limiting steps to this integration. Consideration will also be given to the energy demands of exercise and the implications of this and substrate availability to muscle substrate selection during exercise. This will include some reflection on the mechanistic basis for the decline in muscle fat oxidation that occurs at steady-state exercise intensities over and above 60% maximal oxygen consumption. Finally, the role of increasing muscle acetyl group availability prior to both non-steady state and steady-state exercise on muscle fuel selection during exercise will be addressed.