A limited number of antifungal agents including azoles, polyenes, pyrimidine analogues are used today to combat infections caused by yeast pathogens. While clinical factors can contribute to failures to antifungal treatments, yeast pathogens exposed to these agents can still limit their action either because they are intrinsically resistant or because they acquire specific resistance mechanisms. Microbiological methods are available to measure the susceptibility of yeast pathogens against the existing antifungal agents and to distinguish between antifungal susceptible and antifungal resistant organisms. This distinction can ideally predict the success or failure of a treatment in clinical situations and is available only for a limited number of antifungal agents, i.e. the azole antifungals fluconazole and itraconazole and the pyrimidine analogue 5-fluorocytosine. Cases of antifungal resistance have been reported for almost all classes of antifungal agents, but they have been mainly documented for the pyrimidine analogue 5-fluorocytosine and azole antifungals mainly in Candida species and less frequently in Cryptococcus species. This review summarizes the current knowledge on the different mechanisms of resistance to these agents in these yeast pathogens.