Extensive thermodynamic calculations have been performed for a number of flotation systems of metal sulfide minerals using cyanide as a depressant to investigate the physicochemical principles underlying the effective depression processes. It has been shown that selective depression of the flotation of sulfide minerals by cyanide is achieved through the one or more of the following processes: (A) cyanide dissolves the metal xanthates to form metal-cyanide complexes or combines with surface metal ions to prevent the formation of metal-xanthates; (B) cyanide reduces the redox potential of the flotation pulp and consumes oxygen in the flotation pulp 20 prevent the chemisorption and oxidation of xanthate; (C) cyanide is preferentially adsorbed on the sulphide mineral surfaces as cyanometal complexes to inhibit the adsorption of xanthate and the oxidation of xanthate on mineral surface; (D) cyanide reacts with elemental sulfur and polysulfides to form thiocyanate, thereby removing the surface hydrophobic entity. Electrochemical studies on the pyrite electrode have confirmed the above solution chemistry calculations. It has been found that in cyanide solutions, the surface oxidation of pyrite is greatly enhanced. The initial oxidation step involves the electrochemical adsorption of cyanide on pyrite. This inhibits the adsorption of xanthate on the pyrite surface and minimizes the flotation of pyrite. Furthermore, xanthate adsorbed on pyrite surfaces is readily replaced by cyanide when cyanide is added into the pyrite flotation system.