Insulin-mediated glucose disposal varies at least sixfold in apparently healthy individuals. The adverse effect of decreases in the level of physical fitness on insulin sensitivity is comparable to the untoward impact of excess adiposity, with each accounting for approximately 25% of the variability of insulin action. It is the loss of insulin sensitivity that explains why obese individuals are more likely to develop cardiovascular disease, but not all overweight/obese individuals are insulin resistant. At a clinical level, it is important to identify those overweight individuals who are also insulin resistant and to initiate the most intensive therapeutic effort in this subgroup. Finally, it appears that the adverse impact of overall obesity, as estimated by body mass index, is comparable to that of abdominal obesity, as quantified by waist circumference.