Lead and zinc resources play an essential and important role in all aspects of human social development, and their products are widely used in different fields such as metallurgy, machinery, chemical industry and military. In polymetallic sulfide ores, sphalerite and galena usually coexist closely in the ore. Flotation separation of lead-zinc sulfides is largely achieved by inhibiting sphalerite through the use of inhibitors. Therefore, the study of sphalerite inhibitors is of great significance for achieving efficient separation in lead-zinc flotation. This paper provides a comprehensive overview of the basic research on the inhibition mechanism of sphalerite and the inhibition effects of commonly used reagent systems. It includes inorganic inhibitors (lime, zinc sulfate, cyanide, etc.), organic inhibitors (pectin, locust bean gum, pullulan polysaccharides, tannins, etc.) and novel sphalerite inhibitors such as 2-hydroxyphosphonoacetic acid (HPAA) and 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTCA), as well as combinations of these agents. It also looks forward to the future development direction of lead-zinc separation technology research, which will provide reference for more green and efficient development and utilization of lead-zinc resources.