A number of design strategies exist for the development of novel metalloproteins. These strategies often exploit the inherent symmetry of metal coordination and local topology. Computational design of metal binding sites in flexible regions of proteins is challenging as the number of conformational degrees of freedom is significantly increased. Additionally, without pre-organization of the primary shell ligands by the protein fold, metal binding sites can rearrange according to the coordination constraints of the metal center. Examples of metal incorporation into existing folds, full fold design exploiting symmetry, and fold design in asymmetric scaffolds are presented.