The emergence of drug-resistant fungi poses a continuously increasing threat to human health. Despite advances in preventive care and diagnostics, resistant fungi continue to cause significant mortality, especially in immunocompromised patients. Therapeutic resources are further limited by current usage of only four major classes of antifungal drugs. Resistance against these drugs has already been observed in pathogenic fungi requiring the development of much needed newer antifungal drugs. Epigenetic changes such as DNA or chromatin modifications alter gene expression levels in response to certain stimuli, including interaction with the host in the case of fungal pathogens. These changes can confer resistance to drugs by altering the expression of target genes or genes encoding drug efflux pumps. Multiple pathogens share many of these epigenetic pathways; thus, targeting epigenetic pathways might also identify drug target candidates for the development of broad-spectrum antifungal drugs. In this review, we discuss the importance of epigenetic pathways in mediating drug resistance in fungi as well as in the development of anti-fungal drugs.