Invasive fungal infections carry high morbidity and mortality, but there are no fungal vaccines. In this issue of the JCI, Okaa et al. report that endonuclease 2 (Eng2), an antigen shared by the Blastomyces, Histoplasma, and Coccidioides species of fungi, elicits protective immunity in mice against blastomycosis, histoplasmosis, and coccidioidomycosis. These results establish a common antigen that can elicit protection against multiple mycoses, encouraging the development of a pan-fungal vaccine. The road to fungal vaccines is made difficult by the need for effectiveness in immunocompromised individuals, the sporadic nature of fungal disease, and the economics of vaccine development. Despite these hurdles, there is optimism that such vaccines can be developed and perhaps find usefulness as adjuncts to antifungal therapy.