One important mechanism for functional innovation during evolution is the duplication of genes and entire genomes. Evidence is accumulating that during the evolution of vertebrates from early deuterostome ancestors entire genomes were duplicated through two rounds of duplications (the ‘one-to-two-to-four’ rule). The first genome duplication in chordate evolution might predate the Cambrian explosion. The second genome duplication possibly dates back to the early Devonian. Recent data suggest that later in the Devonian, the fish genome was duplicated for a third time to produce up to eight copies of the original deuterostome genome. This last duplication took place after the two major radiations of jawed vertebrate life, the ray-finned fish (Actinopterygia) and the sarcopterygian lineage, diverged. Therefore the sarcopterygian fish, which includes the coelacanth, lungfish and all land vertebrates such as amphibians, reptiles, birds and mammals, tend to have only half the number of genes compared with actinopterygian fish. Although many duplicated genes turned into pseudogenes, or even ‘junk’ DNA, many others evolved new functions particularly during development. The increased genetic complexity of fish might reflect their evolutionary success and diversity.