BACKGROUND & AIMS: We hypothesize that an optimal and simultaneous provision of energy and protein is favorable to clinical outcome of the critically ill patients. METHODS: We conducted a review of the literature, obtained via electronic databases and focused on the metabolic alterations during critical illness, the estimation of energy and protein requirements, as well as the impact of their administration. RESULTS: Critically ill patients undergo severe metabolic stress during which time a great amount of energy and protein is utilized in a variety of reactions essential for survival. Energy provision for critically ill patients has drawn attention given its association with morbidity, survival and long-term recovery, but protein provision is not sufficiently taken into account as a critical component of nutrition support that influences clinical outcome. Measurement of energy expenditure is done by indirect calorimetry, but protein status cannot be measured with a bedside technology at present. CONCLUSIONS: Recent studies suggest the importance of optimal and combined provision of energy and protein to optimize clinical outcome. Clinical randomized controlled studies measuring energy and protein targets should confirm this hypothesis and therefore establish energy and protein as a power couple.