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Stratospheric ozone depletion through catalytic chemistry involving man‐made chlorofluorocarbons is an area of focus in the study of geophysics and one of the global environmental issues of the twentieth century. This review presents a brief history of the science of ozone depletion and describes a conceptual framework to explain the key processes involved, with a focus on chemistry. Observations that may be considered as evidence (fingerprints) of ozone depletion due to chlorofluorocarbons are explored, and the related gas phase and surface chemistry is described. Observations of ozone and of chlorine‐related trace gases near 40 km provide evidence that gas phase chemistry has indeed currently depleted about 10% of the stratospheric ozone there as predicted, and the vertical and horizontal structures of this depletion are fingerprints for that process. More striking changes are observed each austral spring in Antarctica, where about half of the total ozone column is depleted each September, forming the Antarctic ozone hole. Measurements of large amounts of ClO, a key ozone destruction catalyst, are among the fingerprints showing that human releases of chlorofluorocarbons are the primary cause of this change. Enhanced ozone depletion in the Antarctic and Arctic regions is linked to heterogeneous chlorine chemistry that occurs on the surfaces of polar stratospheric clouds at cold temperatures. Observations also show that some of the same heterogeneous chemistry occurs on the surfaces of particles present at midlatitudes as well, and the abundances of these particles are enhanced following explosive volcanic eruptions. The partitioning of chlorine between active forms that destroy ozone and inert reservoirs that sequester it is a central part of the framework for our understanding of the 40‐km ozone decline, the Antarctic ozone hole, the recent Arctic ozone losses in particularly cold years, and the observation of record midlatitude ozone depletion after the major eruption of Mount Pinatubo in the early 1990s. As human use of chlorofluorocarbons continues to decrease, these changes throughout the ozone layer are expected to gradually reverse during the twenty‐first century.