The basic science and clinical understanding of infection with Blastomyces dermatitidis has been a field of constant evolution and continued revision of hypotheses. This article highlights some areas in which recent progress has the potential for significant impact on the clinical care of patients. Specifically, this article examines the application of modern technology to epidemiologic studies, the development of novel vaccine candidates, emerging populations at risk for the disease, rapid diagnostic tools, and the application of novel antifungal agents in the treatment of blastomycosis.