Polyploidization or whole-genome duplication is a recurring process in evolution. The abundance of polyploidy varies across lineages, evolutionary times, and geographic regions, suggesting that genetics and the environment play a role in the persistence of polyploidy. We utilize various plant and animal model systems at the genus level, including Arabidopsis, Rorippa, Fragaria, Potamogeton, and Neobatrachus, to understand the mechanisms underlying the onset of whole-genome doubling and the subsequent adaptation. After the origin, polyploids face immediate fertility challenges and must adapt mating systems and meiotic machinery to prevent improper chromosome pairing and segregation. We use population genetics approaches to answer particular questions along the polyploidization cycle using various model systems.