Hsp90 is a specialized molecular chaperone that is capable of buffering the expression of abnormal phenotypes. Inhibition of Hsp90 activity results in the expression of these phenotypes that are otherwise masked. Selection of offspring from the crossing of affected progenies results in inheritance and enrichment of these phenotypes, which can become independent of their original stimuli. The current combined evidence favours a model involving the interplay between genetics and epigenetics. The recent proteomics efforts to characterize the Hsp90 interaction networks provide further clues into the molecular mechanisms behind this complex phenomenon. This review summarizes the most recent experimental observations and briefly discusses the genetic and epigenetic views used in explaining the different observations.