Many proteins in living cells coordinate cofactors, such as metal ions, to attain their activity. Since the cofactors in such cases often can interact with their corresponding unfolded polypepticles in vitro, it is important to unravel how cofactors modulate protein folding. In this review, I will discuss the role of cofactors in folding of the blue-copper protein Pseudomonas aeruginosa azurin. In the case of both copper (Cu-11 and Cu-1) and zinc (Zn-11), the metal can bind to unfolded azurin. The residues involved in copper (Cu-11 and Cu-1) coordination in the unfolded state have been identified as Cys112, His-117, and Met121. The affinities of Cu-11, Cu-1, and Zn-11 are all higher for the folded than for the unfolded azurin polypepticle, resulting in metal stabilization of the native state as compared to the stability of apo-azurin. Cu-11, Zn-11, and several apo forms of azurin all fold in two-state kinetic reactions with roughly identical polypepticle-folding speeds. This suggests that the native-state beta-barrel topology, not cofactor interactions or thermodynamic stability, determines azurin's folding barrier. Nonetheless, copper binds much more rapidly (i.e., 4 orders of magnitude) to unfolded azurin than to folded azurin. Therefore, the fastest route to functional azurin is through copper binding before polypepticle folding; this sequence of events may be the relevant biological pathway.