Zinc, a high-performance metallic element, is widely used in industries such as transportation, construction, light industry, machinery, and batteries. In recent years, with the continuous development of the world economy and the continuous expansion of zinc application fields, high-grade and easily selected zinc sulfide mineral resouąrces have gradually become depleted. The efficient recovery and utilization of complex and difficult-to-treat zinc oxide resources has gradually attracted attention. Smithsonite, an important zinc oxide mineral resource, has enormous development potential. Scholars have conducted extensive exploration and research from different perspectives to extract high-grade smithsonite and have recognized that flotation is the most important beneficiation method. This paper provides a brief introduction to the interactions between smithsonite and flotation reagents from the perspective of their properties and crystal structures. Based on this, flotation reagents, including collectors, depressants, and auxiliary reagents, are systematically summarized and evaluated. The most challenging flotation case is selected to outline the current status of the smithsonite flotation process. This study aims to provide insights into the development, discovery, and practical application of flotation reagents and processes for smithsonite.