Problems with organ toxicity from the halogenated volatile anesthetics have influenced clinical practice, anesthetic selection, and drug development for half a century.(1,2) In turn, investigations that elucidated the mechanisms of volatile anesthetics adverse effects identified new mechanisms, provided remarkable insights into human toxicology, and represented seminal contributions to clinical pharmacology. This review focuses on adverse organ effects (hepatic, renal, and others) that are attributable to anesthetic metabolism and/or degradation. Routine reversible effects on pulmonary, cardiac, and other organ functions are not addressed.