In the development of novel sulfide collectors, especially for the low-lime and acid circuits, flotation of chalcopyrite, chalcocite, covellite and pyrite was studied with both new and commercially available S- containing collectors. The natural float- ability of sulfides, water quality, and redox potentials – all of which were considered im- portant in assessing collector strength and selectivity – were also investigated. Chalcopyrite exhibited the highest natural floatability. The response to most collectors, however, was chalcocite > covellite > chalcopyrite > pyrite. Water quality had a very significant effect on both natural and collector-aided floatability. De- ionized water and tap water had a flotation suppression effect compared with doubly- distilled water. Flotation results with single minerals are correlated with those for copper and pyrite from natural ores. Several novel collectors have now been developed for sulfide flotation in acid, neutral or mildly alkaline circuits. The results for four of these collectors, which have shown promise in commercial applications, are discussed in this paper.