Knowledge of energy expenditure is especially important in disease, and may in fact help in the understanding of the pathophysiology of wasting associated with disease. Energy requirements in a clinical setting are often ‘prescribed’ by health professionals, either directly through enteral or parenteral feeding, or perhaps controlled through a hospital diet. Studies initially suggested an increase in energy expenditure, and thus energy requirements, as a direct result of an increase in basal metabolic rate often seen in disease. However, many problems exist in the measurement of BMR in a disease situation, due to the effects of drugs, clinical practice, feeding or possibly anxiety either as a cause of the disease or the measurement itself. These problems could in themselves contribute to the rise in metabolism seen in disease. More recently, however, with the use of tracer techniques such as doubly-labelled water and the bicarbonate–urea method, more accurate estimates of energy expenditure, and thus energy requirements, have been made. Some such measurements have in fact shown that even with an elevated BMR, free-living total energy expenditure can in fact be reduced in many disease situations, suggesting a reduced rather than an increased energy requirement. The present review investigates measurements of total energy expenditure in disease to explore the hypothesis that energy expenditure in disease, even with an elevated BMR, can in fact be reduced due to a concurrent reduction in physical activity.