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Abstract Rezafungin acetate is a novel echinocandin in clinical development for prevention and treatment of invasive fungal infections. Rezafungin is differentiated by a pharmacokinetic/pharmacodynamic (PK/PD) profile that includes a long half‐life allowing once‐weekly administration, front‐loaded plasma drug exposures associated with antifungal efficacy, and penetration into deep‐seated infections, such as intra‐abdominal abscesses. In this series of in vivo studies, rezafungin demonstrated efficacy in the treatment of neutropenic mouse models of disseminated candidiasis, including infection caused by azole‐resistant Candida albicans, and aspergillosis. These results contribute to a growing body of evidence demonstrating the antifungal efficacy and potential utility of rezafungin in the treatment of invasive fungal infections.