The objective of this review paper is to evaluate the impact of undertaking aerobic exercise in the overnight-fasted v. fed-state, in the context of optimising the health benefits of regular physical activity. Conducting a single bout of aerobic exercise in the overnight-fasted v. fed-state can differentially modulate the aspects of metabolism and energy balance behaviours. This includes, but is not limited to, increased utilisation of fat as a fuel source, improved plasma lipid profiles, enhanced activation of molecular signalling pathways related to fuel metabolism in skeletal muscle and adipose tissue, and reductions in energy intake over the course of a day. The impact of a single bout of overnight-fasted v. fed-state exercise on short-term glycaemic control is variable, being affected by the experimental conditions, the time frame of measurement and possibly the subject population studied. The health response to undertaking overnight-fasted v. fed-state exercise for a sustained period of time in the form of exercise training is less clear, due to a limited number of studies. From the extant literature, there is evidence that overnight-fasted exercise in young, healthy men can enhance training-induced adaptations in skeletal muscle metabolic profile, and mitigate against the negative consequences of short-term excess energy intake on glucose tolerance compared with exercising in the fed-state. Nonetheless, further long-term studies are required, particularly in populations at-risk or living with cardio-metabolic disease to elucidate if feeding status prior to exercise modulates metabolism or energy balance behaviours to an extent that could impact upon the health or therapeutic benefits of exercise.