Understanding the regulation of appetite and energy expenditure mechanisms is essential for the health and disease. The recognition that the distribution of these regulatory mechanisms plays a central role in the pathogenesis of obesity and associated metabolic syndrome is not new, and it is even more interesting to understand what happens in an obese patient in the Intensive Care Unit (ICU). This review focuses on the catabolic role of orexin, which paradoxically coexists with its anabolic feeding-inducing role. The goal of this review is to provide insight into the biological mechanism governing orexin’s role in energy expenditure, discuss its significance in the context of ICU. Mammals possess a specialized tissue termed Brown Adipose Tissue (BAT) that expends calories to counteract hypothermia. The ability to enhance energy expenditure by manipulating BAT activity is attractive from a therapeutic standpoint, in light of the discovery of metabolically active BAT in adult humans. The finding of a relationship between BAT and orexins levels suggests new research on the possible roles of orexins in many anomalies of energy expenditure, including those of obese patients in the ICU.