Studies have yielded discrepant results concerning whether the thermic effect of food (TEF) is reduced in obesity. Methodological variations among published studies make understanding the discrepant results very difficult. Although methodological differences are often noted as contributing to the discrepant results, little work has been done to address these differences and standardize experimental protocols. This paper reviews 50 studies that have investigated TEF in obesity and focuses on factors related to experimental protocol and subject control that reportedly affect measurements of resting energy expenditure, postprandial energy expenditure, and the calculation of TEF.