Traditionally, the folding of disulfide-rich proteins has been seen as a special case of protein folding, considered apart from the well studied small two-states folding proteins.In most cases, the studies on disulfide-rich proteins have been focused on the pure description of the different species occurring along the process and in their kinetic of inter-conversion, but little attention has been paid to key aspects such as.thermodynamics, structural characterization of folding intermediates or in silico prediction of folding pathways.We have addressed these issues using different protein models to shed some light on the rules driving the folding of disulfide-rich proteins.The results illustrate a high level of diversity in folding mechanisms, differing in the heterogeneity and native disulfide-bond content of their intermediates.Nevertheless, our data suggest that the forces governing the folding of small disulfide-rich proteins do not differ much from those governing the acquisition of the functional conformation in small proteins without disulfide bonds, i.e.the establishment of native-like interactions between elements of secondary structure.This observation will be of help in joining the theoretical discontinuity between the folding of disulfide-free and disulfide-containing proteins and permits to advance towards a unified theory of protein folding.