As an important strategic non-metallic mineral resource, fluorite has been widely used in various industrial fields, such as metallurgy, optics and semiconductor manufacturing, as well as fluorine-related chemical engineering. Since the major gangue minerals of fluorite ore are silicate and carbonate ones, flotation is the main beneficiation method for the concentration. Compared with the relatively easy operation for silicate-type fluorite ore, fluorite concentration from calcite has always been the most difficult challenge in the field of mineral processing. In this review, analyses of the fundamental reasons for the difficulties of flotation separation of fluorite from calcite are performed, from the similar surface properties of both calcium minerals to the deterioration by the interference of dissolved ions in the pulp during grinding and flotation. Recent achievements in the flotation separation of fluorite from calcite as the main contents are comprehensively summarized, covering all aspects of flotation reagents of collectors, depressants and modifiers. Finally, successful examples of industrial practices forfluorite and calcite flotation separation are introduced. This overview provides a detailed and comprehensive reference source for the current research status of fluorite and calcite flotation separation, and some suggestions for future research are provided.