Abstract: In this paper, the application development of organic macromolecular depressants in the beneficiation of polymetallic sulfide ores was summarized from the natural polymers and synthetic polymers. The depressant mechanisms and its adsorption patterns on sulfide ores were introduced. Practical application cases were used to elaborate the application development of natural and synthetic macromolecule depressants. The future development trend of organic macromolecular depressants was also predicted by the overview of the current application status of macromolecular depressants.