Modern trends in technological improvement for producing high-quality rhenium-containing molybdenum concentrates are aimed at developing environmentally friendly solutions com-pared to traditional ones, involving a reduction in consumption or complete replacement of toxic substances and the use of plant reagents and microorganisms and make it possible to eliminate energy-intensive processes of steaming and roasting. It is known that up to 25%–30% of Mo, Cu and Re goes to rough flotation tailings and is lost in wastes. Those losses are a consequence of the ore composition variability, chalcopyrite–molybdenite ratio, an increase in the proportion between primary copper sulfide and finely disseminated molybdenite and the recovery of floating pyrite. High rates of valuable metal recovery into bulk concentrate can be achieved by using new compositions of flotation reagents that selectively change the hydrophobic properties of the target minerals. The application of new reagent compositions, including novel chemicals—dithiopyrylmethane (DTM), composite reagent (CR) and conventional butyl xanthate (ButX)—was theoretically and experimentally substantiated for the effective rhenium extraction in the processing of hard-to-beneficiate complex molybdenum ores. It is identified that DTM forms a complex DTM–Re compound and chemically adsorbed on rhenium-containing molybdenite providing an increase in Re recovery into the bulk Cu–Mo–Re concentrate by 17%, reducing by two times the loss of rhenium with flotation tailings, and the subsequent 97.6% Re extraction of the molybdenum concentrate by autoclave leaching.