The study of energy expenditure (EE) has deep roots in understanding aging and lifespan in all species. In humans, total EE decreases substantially in advanced age resulting from parallel changes in resting metabolic rate (RMR) and activity EE. For RMR, this reduction appears to be due to a reduction in organ mass and specific metabolic rates of individual tissues. However, these anatomical changes explain very little regarding the decline in activity EE, which is governed by both genetic and environmental sources. The biological control centers for activity EE are closely coupled with body mass fluctuations and seem to originate in the brain. Several candidate neuromodulators may be involved in the age-related reduction of activity EE that include: orexin, agouti-related proteins and dopaminergic pathways. Unfortunately, the existing body of research has primarily focused on how neuromodulators influence weight gain and only a few studies have been performed in aging models. Recent evidence suggests that activity EE has an important role in dictating lifespan and thus places emphasis on future research to uncover the underlying biological mechanisms. The study of EE continues to unlock clues to aging.