Tungsten is the importantly rare and strategic metal and plays an irreplaceable role in the military, civil, industrial, and other fields. Scheelite and wolframite account for approximately 70% and 30% of the world’s total tungsten resources, respectively. Tungsten minerals are mainly enriched through froth flotation, especially scheelite. However, the selective separation of scheelite from the other Ca-containing minerals is still a worldwide problem due to their similar surface properties. Achieving precise regulation of interfacial physicochemical properties constitutes the scientific foundation for successful scheelite flotation. It is the key to develop excellent flotation reagents with good collecting ability and high selecting. Therefore, tungsten flotation reagent and its molecular design, synergistic effect and interfacial assembly of flotation reagents and metal ion coordination regulation of molecular assembly are introduced in detail.