The environmental mold Aspergillus fumigatus causes invasive aspergillosis in humans and has historically been associated with mortality rates as low as 25% and as high as 90% in high-risk patients, including stem cell and organ transplant recipients. Triazole antifungals, such as voriconazole, are first line therapy and have greatly improved survival since their introduction; however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased mortality and treatment failure. Resistance markers associated with environmental triazole fungicide use rather than previous patient exposure to antifungals have raised particular clinical and public health concern. Reports of triazole resistant A. fumigatus have increased worldwide in the past 15 years, and the first U.S. human isolates of fungicide-associated resistant A. fumigatus were described in 2016. Here we review the clinical experience, changing epidemiology, and implications of the two major routes of resistance development in A. fumigatus.