The increasing incidence of invasive fungal infections is the result of many factors, including an increasing number of patients with severe immunosuppression. Although new drugs have been introduced to combat this problem, the development of resistance to antifungal drugs has become increasingly apparent, especially in patients who require long-term treatment or who are receiving antifungal prophylaxis, and there is growing awareness of shifts of flora to more-resistant species. The frequency, interpretation, and, in particular, mechanism of resistance to current classes of antifungal agents, particularly the azoles (where resistance has climbed most prominently) are discussed in this review.