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Invasive fungal infections are a strong contributor to healthcare costs, morbidity and mortality, especially amongst hospitalized patients. Historically, Candida was responsible for approximately 15% of all nosocomial bloodstream infections. In the past 10 years, the epidemiology of Candida species has altered, with increasing prevalence of resistant species. With rising fungal resistance, especially in Candida spp., the demand for novel antifungal therapies has exponentially increased over the last decade. Newer antifungal agents have become an attractive option for patients needing long-term therapy for infections or those requiring antifungal prophylaxis. Despite advances in coverage of non-Candida pathogens with newer agents, clinical scenarios involving multidrug-resistant fungal pathogens continue to arise in practice. Combination antifungal therapy can lead to a host of side-effects, some of which can be drug limiting. Additional antifungal therapies with enhanced fungal spectrum of activity and decreased rates of adverse effects are warranted.