Predictive methods for the computational design of proteins search for amino acid sequences adopting desired structures that perform specific functions. Typically, design of 'function' is formulated as engineering new and altered binding activities into proteins. Progress in the design of functional protein-protein interactions is directed toward engineering proteins to precisely control biological processes by specifically recognizing desired interaction partners while avoiding competitors. The field is aiming for strategies to harness recent advances in high-resolution computational modeling-particularly those exploiting protein conformational variability-to engineer new functions and incorporate many functional requirements simultaneously.