For over two centuries, scientists have measured gas exchange in animals and humans and linked this to energy expenditure of the body. The aim of this review is to provide a comprehensive overview of open-circuit diluted flow indirect calorimetry and to help researchers to make the optimal choice for a certain system and its application. A historical perspective shows that ‘open circuit diluted flow’ is a technique first used in the 19th century and applicable today for room calorimeters, ventilated hood systems, and facemasks. Room calorimeters are a classic example of an open-circuit diluted flow system. The broadly applied ventilated hood calorimeters follow the same principle and can be classified as a derivative of these room calorimeters. The basic principle is that the subject breathes freely in a passing airflow that is fully captured and analyzed. Oxygen and CO 2 concentrations are measured in inlet ambient air and captured outlet air. The airflow, which is adapted depending on the application (e.g., rest versus exercise), is measured. For a room indirect calorimeter, the dilution in the large room volume is also taken into account, and this is the most complex application of this type of calorimeter. Validity of the systems can be tested by alcohol burns, gas infusions and by performing repeated measurements on subjects. Using the latter, the smallest CV (%) was found for repeated V O 2max tests (1.2%) with an SD of approximately 1 kJ min −1 . The smallest SD was found for sleeping metabolic rate (0.11 kJ min −1 ) with a CV (%) of 2.4%.