The ray-finned fishes are the most diverse and successful within the vertebrates and their genomes vary widely in size. Previous studies suggested that two rounds of genome duplications have been involved in vertebrate evolution. The recent studies on comparative genomics have further suggested that a third round of fish-specific genome duplication (FSGD) in ray-finned (actinopterygian) fishes might have occurred at about 350 million years ago, during the divergence between teleost fish and basal actinopterygian lineages. Therefore, FSGD might be related to the increase in species number and biological diversity during this time. Further studies on comparative genomics and functional genomics will be needed to confirm the hypothesis.