Whole genome duplication (leading to polyploidy) is widely accepted as an important evolutionary force in plants, but it is less recognized as a driver of animal diversification. Nevertheless, it occurs across a wide range of animals; this review investigates why it is particularly common in fish and amphibians, while rare among other vertebrates. We review the current geographic, ecological and phylogenetic distributions of sexually reproducing polyploid taxa before focusing more specifically on what factors drive polyploid formation and establishment. In summary, (1) polyploidy is phylogenetically restricted in both amphibians and fishes, although entire fish, but not amphibian, lineages are derived from polyploid ancestors. (2) Although mechanisms such as polyspermy are feasible, polyploid formation appears to occur principally through unreduced gamete formation, which can be experimentally induced by temperature or pressure shock in both groups. (3) External reproduction and fertilization in primarily temperate freshwater environments potentially exposes zygotes to temperature stress, which can promote increased production of unreduced gametes. (4) Large numbers of gametes and group breeding in relatively confined areas could increase the probability of compatible gamete combinations in both groups. (5) Both fish and amphibians have a propensity to form reproductively successful hybrids; although the relative frequency of autopolyploidy versus allopolyploidy is difficult to ascertain, multiple origins involving hybridization have been confirmed for a number of species in both groups. (6) Problems with establishment of polyploid lineages associated with minority cytotype exclusion could be overcome in amphibians via assortative mating by acoustic recognition of the same ploidy level, but less attention has been given to chemical or acoustic mechanisms that might operate in fish. (7) There is no strong evidence that polyploid fish or amphibians currently exist in more extreme environments than their diploid progenitors or have broader ecological ranges. (8) Although pathogens could play a role in the relative fitness of polyploid species, particularly given duplication of genes involved in immunity, this remains an understudied field in both fish and amphibians. (9) As in plants, many duplicate copies of genes are retained for long periods of time, indicative of selective maintenance of the duplicate copies, but we find no physiological or other reasons that could explain an advantage for allelic or genetic complexity. (10) Extant polyploid species do not appear to be more or less prone to extinction than related diploids in either group. We conclude that, while polyploid fish and amphibians share a number of attributes facilitating polyploidy, clear drivers of genome duplication do not emerge from the comparison. The lack of a clear association of sexually reproducing polyploids with range expansion, harsh environments, or risk of extinction could suggest that stronger correlations in plants may be driven by shifts in mating system more than ploidy. However, insufficient data currently exist to provide rigorous tests of these hypotheses and we make a plea for zoologists to also consider polyploidy as a possibility in continuing taxonomic surveys.