The assignment of protein domains from three-dimensional structure is critically important in understanding protein evolution and function. Domains are quasi-independent substructures that are thought to fold autonomously, to carry specific molecular functions, to move relative to each other as semi-rigid bodies and to speed the evolution of new functions by recombination. The concepts underlying computational methods for locating domains in three-dimensional structures are presented. Early algorithms focused on physical criteria to identify compact subunits. With the growth of the structural database, the focus has shifted to methods for identifying recurrent substructures that can form the basis for a consistent protein-structure classification.