Use of helium-oxygen (He/O2) mixtures in critically ill patients is supported by a reliable and well understood theoretical rationale and by numerous experimental observations. Breathing He/O2 can benefit critically ill patients with severe respiratory compromise mainly by reducing airway resistance in obstructive syndromes such as acute asthma and decompensated chronic obstructive pulmonary disease. However, the benefit from He/O2 in terms of respiratory mechanics diminishes rapidly with increasing oxygen concentration in the gaseous mixture. Safe use of He/O2 in the intensive care unit requires specific equipment and supervision by adequately experienced personnel. The available clinical data on inhaled He/O2 mixtures are insufficient to prove that this therapy has benefit with respect to outcome variables. For these reasons, He/O2 is not currently a standard of care in critically ill patients with acute obstructive syndromes, apart from in some, well defined situations. Its role in critically ill patients must be more precisely defined if we are to identify those patients who could benefit from this therapeutic approach.