Fuel homeostasis and blood glucose levels are remarkably well maintained during exercise in healthy individuals. However, in insulin-dependent diabetics, the very basis for fuel homeostasis adjustments, i.e., a normal endogenous insulin production, is absent. The metabolic alterations characterizing diabetes may, therefore, under certain circumstances lead to pertubations of fuel homeostasis. Thus, exercise in the hyper-insulinemic patients may result in hypoglycemic reactions and, in hypoinsulinemic patients, in increased blood glucose levels. In addition, diabetes mellitus is associated with peripheral insulin resistance, which may result in a deterioration of the overall glucose homeostasis and consequently make the treatment more difficult to manage. Regular physical activity has been shown to normalize the peripheral insulin resistance in insulin-dependent diabetics. Knowledge about these responses is important in order to enable this patient group to participate in physical activities on the same conditions as non-diabetics. However, advice on how insulin-dependent diabetics should adjust insulin or diet before exercise is difficult to give due to high interindividual variability in response to exercise. Thus, individualized recommendations for exact treatment modification in association with exercise are necessary.