Genome sequences from the pufferfishes Takifugu rubripes (Fugu) and Tetraodon nigroviridis, the zebrafish Danio rerio and the medaka Oryzias latipes together with genomic data from various other fish species have opened an important era of comparative genomics shedding a new light on the structure and evolution of vertebrate genomes. For instance, comparative analysis of fish genomes has revealed that the ancestral bony vertebrate genome was composed of 12 chromosomes, has confirmed the occurrence of at least one event of genome duplication in the early history of vertebrates and has allowed the identification of conserved regulatory and coding sequences in the human genome. Importantly, major differences have been observed between teleost fish and mammalian genomes. There is now convincing evidence that all teleosts are derived from a common tetraploid fish ancestor. This tetraploidization event arose about 320-350 million years ago in the ray-finned fish lineage, followed by rediploidization and retention of hundreds of duplicate pairs. Divergent evolution of the resulting duplicates has been proposed to be involved in the species richness observed in teleost fishes. Fish genomes also contain many more families of transposable elements than mammals and birds. Finally, while the mammalian and bird lineages possess major sex determination systems with sex chromosomes conserved in very divergent species, fishes have very frequently switched between sex determination mechanisms and repeatedly created novel sex chromosomes during evolution. Hence, teleost fishes display a high level of genomic plasticity, which might be related to the astonishing biodiversity observed in these animals.