Appropriate nutrition in the hospital setting, particularly in critically ill patients, has long been tied to improving clinical outcomes. During critical illness, inflammatory mediators and cytokines lead to the creation of a catabolic state to facilitate the use of endogenous energy sources to meet increased energy demands. This process results in increasing the likelihood of overfeeding. The literature has revealed exponential advances in understanding the molecular basis of nutritional support and evolution of clinical protocols aimed at treating artificial nutritional support as a therapeutic intervention, preventing loss of lean body mass and metabolic deterioration to improve clinical outcomes in the critically ill.