To maintain protein homeostasis, a variety of quality control mechanisms, such as the unfolded protein response and the heat shock response, enable proteins to fold and to assemble into functional complexes while avoiding the formation of aberrant and potentially harmful aggregates. We show here that a complementary contribution to the regulation of the interactions between proteins is provided by the physicochemical properties of their amino acid sequences. The results of a systematic analysis of the protein-protein complexes in the Protein Data Bank (PDB) show that interface regions are more prone to aggregate than other surface regions, indicating that many of the interactions that promote the formation of functional complexes, including hydrophobic and electrostatic forces, can potentially also cause abnormal intermolecular association. We also show, however, that aggregation-prone interfaces are prevented from triggering uncontrolled assembly by being stabilized into their functional conformations by disulfide bonds and salt bridges. These results indicate that functional and dysfunctional association of proteins are promoted by similar forces but also that they are closely regulated by the presence of specific interactions that stabilize native states.