A variety of methodologies are under development to alter the behavior of existing metal centers or create entirely new sites within a protein framework in order to exploit the intrinsic chemical versatility of metals using the exquisite level of control that a protein matrix can exert to modulate their reactivity. Even at this relatively early stage, engineering of metal centers has led to the development of a number of emerging technologies with a wide variety of applications, including affinity purification of proteins, engineering of metal-mediated protein stability, control of protein activity, imaging and therapy, biosensors, and new catalysts.