Despite the long and successful history of vaccine use, primarily for viral diseases, fungal pathogens have only rarely been considered as targets for vaccination. To date, only one antifungal vaccine, designed to prevent ringworm in cattle, has progressed beyond the experimental stage. W�thrich et al. now describe the use of a live attenuated strain of Blastomyces dermatitidis to prevent blastomycosis, an often-fatal yeast infection of the lung. Mice immunized with killed wild-type B. dermatitidis mount an immune response to one of its major cell surface adhesion proteins, WI-1, but they are only weakly protected when challenged with the live pathogen. W�thrich and coworkers previously took advantage of the tractable genetics of this yeast to create a strain lacking the WI-1 gene, showing that this strain could not propagate or cause disease in mice Here, they report that live WI-1- yeast provoke a T cell response that protects inoculated animals from infection with wild-type B. dermatitidis. Crucially, this protection applies not only against yeast that are isogenic to the attenuated strain, but also to several unrelated pathogenic isolates. The authors also show that fungal cell wall preparations derived from the WI-1- strain also protect mice from lung infections, raising the possibility that, as with the live attenuated organism, one or more purified fungal components could be used as an effective vaccine.