Abstract Objectives Rezafungin is a novel echinocandin with a unique structural configuration enabling weekly IV dosing. We report on early use of rezafungin in our outpatient parenteral antibiotic therapy (OPAT) service, reviewing indications, treatment regimens, outcomes and adverse events in adult patients receiving rezafungin at a tertiary infectious disease centre. We also review published cases of rezafungin use, licensing trials, spectrum and pharmacokinetics/pharmacodynamics and how that might relate to its propensity to generate resistance (in comparison with daily echinocandins). Methods All adult patients who received rezafungin therapy via the OPAT service in 2024–25 were included. Patient demographics, infections, treatment regimens and outcomes were recorded. Results Six patients (age range 30–84 years) received rezafungin therapy between July 2024 and February 2025. Indications included invasive and mucocutaneous candidiasis, predominantly caused by azole-resistant Candida species. We also report the first case of using rezafungin in combination with voriconazole to treat azole-refractory pulmonary aspergillosis. Rezafungin courses were a median length of 4 doses (range: 2–5) and were generally well tolerated with no laboratory adverse events. Reasons for choosing rezafungin over daily echinocandins were patient preference/convenience (n = 5), concern regarding azole resistance (n = 4) and facilitation of earlier discharge (n = 2). One hundred and fifty-seven days with an IV catheter were saved through once-weekly dosing. Outcomes were positive, with all patients showing mycological clearance. Conclusions Early use of rezafungin at our centre and in the international literature suggests it is a well-tolerated, convenient and useful addition to the antifungal armamentarium, particularly in the outpatient setting.