The liver plays a pivotal role in a myriad of metabolic processes, including detoxification, glycolipidic storage and export, and protein synthesis. Breath tests employing (13)C as stable isotope have been introduced to explore such energy-dependent pathways involving mitochondrial function in the liver. Specific substrates are ketoisocaproic acid, methionine, and octanoic acid. In humans, the application of (13)C-breath tests ranges from nonalcoholic and alcoholic liver diseases to liver cirrhosis, hepatocarcinoma, preoperative and postoperative assessment of liver function, and drug-induced liver damage. Studying liver mitochondrial function by (13)C-breath tests represents a complementary tool to monitor complex metabolic processes in health and disease.