Abstract Most dimorphic fungal pathogens cause respiratory disease in mammals and must therefore possess virulence mechanisms to combat and overcome host pulmonary defenses. Over the past decade, advances in genetic tools have made it possible to investigate the basis of dimorphic fungal pathogenesis at the molecular level. Gene disruptions and RNA interference have now formally demonstrated the involvement of six virulence factors: CBP, α-(1,3)-glucan, BAD1, SOWgp, Mep1, and urease. Additional candidate virulence-associated genes have been identified on the premise that factors necessary for pathogenicity are associated specifically with the parasitic form. This principle continues to form the foundation for genomics-based analyses to further augment the list. Thus, the stage is set and the tools are in place for the next phase of medical mycology research: defining the virulence-associated factors underlying the success of dimorphic fungal pathogens.