Typically, two catalysts are needed for this reaction: a zerovalent palladium complex and a copper(I) halide salt. Common examples of palladium catalysts include those containing phosphine ligands such as Tetrakis(triphenylphosphine)palladium(0)|. Another commonly used palladium source is [, but complexes containing bidentate phosphine ligands, such as , , and (1,1'-Bis(diphenylphosphino)ferrocene)palladium(II) dichloride| have also been used. The drawback to such catalysts is the need for high loadings of palladium (up to 5 mol %), along with a larger amount of a copper co-catalyst. 
Pd complexes are in fact pre-catalysts since they must be reduced to Pd before catalysis can begin. Pd complexes generally exhibit greater stability than Pd complexes and can be stored under normal laboratory conditions for months. Pd catalysts are reduced to Pd in the reaction mixture by an amine, a phosphine ligand, or another reactant in the mixture allowing the reaction to proceed. For instance, oxidation of triphenylphosphine to triphenylphosphine oxide can lead to the formation of Pd in situ when  is used.
Copper(I) salts, such as CuI, react with the terminal alkyne and produce a copper(I) acetylide, which acts as an activated species for the coupling reactions. Cu(I) is a co-catalyst in the reaction, and is used to increase the rate of the reaction.