The recognition that certain long-known nonchromosomal genetic elements were actually prions was based not on the specific phenotypic manifestations of those elements, but rather on their unusual genetic properties. Here, we outline methods of prion assay, methods for showing the nonchromosomal inheritance, and methods for determining whether a nonchromosomal trait has the unusual characteristics diagnostic of a prion. Finally, we discuss genetic methods often useful in the study of yeast prions.