Since it was developed in the 1960s, the carbon dioxide (CO2) laser has had an important role in the practice of dermatology. The CO2 laser has some advantages over conventional techniques used in dermatologic surgical treatment. It routinely provides a bloodless surgical field as well as unusual surgical precision. Although the CO2 laser is specifically indicated for certain conditions, in other situations, only marginal benefit may be noted in comparison with standard techniques such as scalpel surgical procedures, dermabrasion, cryosurgery, and electrosurgery. In this article, we briefly review the history and physics of the CO2 laser, its operation, and safety principles and discuss dermatologic conditions that are treated with the CO2 laser. We also describe 8 representative cases from our experience with more than 800 cases of CO2 laser treatment in the practice of dermatology at the Mayo Clinic since 1986.