Abstract: Chalcopyrite and molybdenite are often associated in porphyry deposits, and they have very similar floatability. Therefore, the flotation separation between chalcopyrite and molybdenite has become important and difficult points. Flotation technology is a common method for the separation of chalcopyrite and molybdenite, and flotation reagents are critical to control the separation efficiency. Based on the crystal structure, surface wettability, surface electrical properties and other physicochemical properties of chalcopyrite and molybdenite, the separation difficulties were analyzed. In addition, the process of copper-molybdenum separation and the research development of flotation reagents were discussed systematically. The future development of flotation separation of chalcopyrite and molybdenite was prospected. The aim of the paper is to provide references for peers.