The safety of anesthesia, which is an important step for surgery, can be determined by its impact on oxidative stress and inflammation. The effects of volatile anesthetics such as isoflurane and sevoflurane on oxidative stress and inflammation are reviewed in various (1) cell lines, (2) rodents, and (3) human studies. Isoflurane and sevoflurane are reported to have antioxidant and anti-inflammatory effects in all cells with exception of neuronal cell lines. In addition, various animal studies have indicated that isoflurane and sevoflurane were not only safe but also reduced oxidative stress and inflammation in rodent models. In human studies, oxidative stress, inflammation, and DNA damage were not affected by isoflurane and sevoflurane in patients undergoing minor incision surgeries. On the other hand, elevated oxidative stress, inflammation, and DNA damage have been observed in patients undergoing major surgeries such as abdominal and orthopedic surgeries, hysterectomy, cholecystectomy, and thoracotomy. Although impact of anesthetics on oxidative stress and inflammation is still not clear due to the variations of patients' health conditions, types of surgery and the quantities of anesthetics, isoflurane, and sevoflurane can be considered safe anesthetics with respect to their effect on oxidative stress and inflammation in subjects undergoing minor surgery. Continuous effort evaluating the safety of anesthesia in various aspects is required.