Yeast prions have been proposed to act as epigenetic determinants, generating new phenotypic traits that may promote yeast survival. However, this was controversial, as prions had not been found in wild yeasts. Here, Lindquist and colleagues confirm that prions do exist in wild strains and can confer phenotypic changes. By testing 690 wild strains of Saccharomyces from diverse niches, they were able to identify [PSI+] and [MOT3+] in a small number of yeasts. Both prions could cause phenotypic changes, which could be beneficial or detrimental, depending on the circumstances. Interestingly, meiotic re-assortment of endogenous genetic variation led to fixation of one [PSI+]-dependent trait in some strains, making it prion independent. Moreover, wild strains harboured other prions that caused phenotypic changes and could be transferred to other strains via cytoplasmic transfer.