Pathogenic fungi are an increasing public health concern. The emergence of antifungal resistance coupled with the scarce antifungal arsenal highlights the need for novel therapeutics. Fortunately, the past few years have witnessed breakthroughs in antifungal development. Here, we discuss pivotal interdisciplinary approaches for the discovery of novel compounds with efficacy against diverse fungal pathogens. We highlight breakthroughs in improving current antifungal scaffolds, as well as the utility of compound combinations to extend the lifespan of antifungals. Finally, we describe efforts to refine candidate chemical scaffolds by leveraging structure-guided approaches, and the use of functional genomics to expand our knowledge of druggable antifungal targets. Overall, we emphasize the importance of interdisciplinary collaborations in the endeavor to develop innovative antifungal strategies.