We can now assign about two thirds of the sequences from completed genomes to as few as 1400 domain families for which structures are known and thus more ancient evolutionary relationships established. About 200 of these domain families are common to all kingdoms of life and account for nearly 50% of domain structure annotations in the genomes. Some of these domain families have been very extensively duplicated within a genome and combined with different domain partners giving rise to different multidomain proteins. The ways in which these domain combinations evolve tend to be specific to the organism so that less than 15% of the protein families found within a genome appear to be common to all kingdoms of life. Recent analyses of completed genomes, exploiting the structural data, have revealed the extent to which duplication of these domains and modifications of their functions can expand the functional repertoire of the organism, contributing to increasing complexity.