The C−N cross-coupling chemistry intensely developed since the late 1990s has supplied synthesists with an overwhelming number of methods to effectively combine carbon and nitrogen residues. This new chemistry relies on complexes of mainly two metals, copper and palladium, used as catalysts or stoichiometric agents. The development of new methods has revealed both similarities and differences in the principles used for the design of new catalytic systems and analysis of their reactivity and selectivity. The discussion of cross-coupling chemistry of these two metals can be performed within a common mechanistic paradigm, helping to elucidate the key factors governing the behavior of the transition-metal complexes involved.