Polyploidization via whole-genome duplications (WGD) is a common phenomenon in organisms. However, investigations into this phenomenon differ greatly between plants and animals. Recent research on polyploid plants illustrates the immediate changes that follow WGDs and the mechanisms behind in both genetic and epigenetic consequences. Unfortunately, equivalent questions remain to be explored in animals. Enlightened by botanical research, the study of polyploidization in vertebrates involves the identification of model animals and the establishment of strategies. Here we review and compare the research on plants and vertebrates while considering intrageneric or intraspecific variation in genome size. Suitable research methods on recently established polyploidy systems could provide important clues for understanding what happens after WGDs in vertebrates. The approach yields insights into survival and the rarity of polyploidization in vertebrates. The species of Carassius and the allopolyploid system of goldfish x common carp hybridization appear to be suitable models for unraveling the evolution and adaptation of polyploid vertebrates.