Breath tests are attractive since they are noninvasive and can be repeated frequently in the dynamically changing state of critically ill patients. Volatile organic compounds can be produced anywhere in the body and are transported via the bloodstream and exhaled through the lung. They can reflect physiologic or pathologic biochemical processes such as lipid peroxidation, liver disease, renal failure, allograft rejection, and dextrose or cholesterol metabolism. This review describes the diagnostic potential of endogenous organic volatile substances in the breath of critically ill patients. Since many of these patients require ventilatory support, aspects of breath analysis under mechanical ventilation will be addressed. Analytical procedures, problems concerning the physiologic meaning of breath markers and future developments will be discussed.