Candida infections have increased due to the growth and expansion of susceptible patient populations. The azole fluconazole is the most widely prescribed antifungal, but rising rates of clinical resistance among Candida glabrata isolates have greatly limited its utility. A better understanding of the mechanisms of azole antifungal resistance will provide information needed to overcome this clinical problem and reclaim this antifungal class as an option for empiric treatment of Candida infections. By far, the most frequent mechanism of azole resistance in C. glabrata is the overexpression of multidrug transporters due to activating mutations in the gene encoding transcription factor Pdr1. In this review, we will discuss the molecular and genetic basis of azole resistance in C. glabrata with particular attention given to the most recent discoveries in this field.