Abstract: Lead and zinc resources are strategic mineral resources in China, and flotation is a common separation method for lead-zinc sulfide minerals. The relationship between the crystal structure and floatability of lead-zinc sulfide minerals was introduced, the influence of pulp environment on lead-zinc minerals flotation separation from the aspects of flotation electrochemical theory and quantum chemistry theory was analyzed, the mechanism of the interaction between reagents and the surface of lead-zinc minerals from the molecular point of view was summarized, and the flotation technology of lead-zinc minerals separation and the application of reagents in production were also summarized. At present, it is difficult to recover lead-zinc minerals resources and there is a lack of novel reagents. Therefore, deeply revealing the mechanism of reagents action and developing new green reagents are one of the research directions of lead-zinc minerals separation in the future.