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Optimal nutritional therapy has been associated with better clinical outcomes and requires providing energy as closed as possible to measured energy expenditure. We reviewed the current innovations in energy expenditure assessment in humans, focusing on indirect calorimetry and other new alternative methods.Although considered the reference method to measure energy expenditure, the use of indirect calorimetry is currently limited by the lack of an adequate device. However, recent technical developments may allow a broader use of indirect calorimetry for in-patients and out-patients. An ongoing international academic initiative to develop a new indirect calorimeter aimed to provide innovative and affordable technical solutions for many of the current limitations of indirect calorimetry. New alternative methods to indirect calorimetry, including CO2 measurements in mechanically ventilated patients, isotopic approaches and accelerometry-based fitness equipments, show promises but have been either poorly studied and/or are not accurate compared to indirect calorimetry. Therefore, to date, energy expenditure measured by indirect calorimetry remains the gold standard to guide nutritional therapy.Some new innovative methods are demonstrating promises in energy expenditure assessment, but still need to be validated. There is an ongoing need for easy-to-use, accurate and affordable indirect calorimeter for daily use in in-patients and out-patients.