Few dietary components are surrounded by more misinformation and myths than the calorie. This confusion can be attributed in part to a lack of accurate and practical methods for assessing energy intake and thus requirements in humans over periods extending beyond several days. The availability of modern respiratory-chamber indirect calorimetry systems and results from human studies with doubly labeled water are now helping to clarify uncertainties surrounding energy requirements. We describe studies of patients with endogenous obesity as an example of how these research methods are resolving long-standing questions regarding energy requirements. The results of these investigations reveal some of the flaws in estimating energy requirements by self-report methods. Advances in accurately measuring energy expenditure are making important contributions to the study of human energy requirements and are providing new and important research opportunities.