The primary cause of common human obesity remains uncertain. There are several plausible explanations, including the popular “carbohydrate-insulin” model (CIM), which suggests that body-fat gain results from consumption of carbohydrates that stimulate postprandial insulin, which promotes energy storage and further intake in a vicious cycle. The theoretical basis of the CIM has been refuted by several recent experiments. We suggest that although insulin plays an important role in body fat regulation, the CIM fails because it focuses on the direct action of insulin on adipose tissue after the consumption of a meal containing carbohydrates. Rather, we propose that the role of insulin in obesity may be better understood by considering its pleiotropic action on multiple organs that is driven by factors mostly independent of carbohydrate intake. Reconsidering the role of insulin may improve our understanding of the causes of obesity and its treatment.