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Zygomycosis is a frequently lethal invasive infection in high-risk patients such as the immunocompromised [especially haematopoietic stem cell transplant (HSCT) recipients] and patients with type 2 diabetes mellitus. However, zygomycosis has also been reported in individuals without known risk factors. The causative fungi are members of the order Mucorales and individual species within this group require a high level of laboratory skill for their identification. These organisms are resistant to voriconazole and also to the echinocandins, and although zygomycosis is less commonly documented than invasive aspergillosis in leukaemic and HSCT patients, there are recent reports suggesting that it has increased in incidence since the introduction of voriconazole. Zygomycosis can present clinically as rhinocerebral, pulmonary or disseminated disease which progresses rapidly. The management of cases is based on early diagnosis, surgical debridement when possible and aggressive antifungal therapy. Based on clinical experience, but without the benefit of comparative studies, liposomal amphotericin B has become the therapeutic agent of choice. Posaconazole is a new orally administered triazole antifungal and the first member of this class to have comparable in vitro activity to amphotericin B against most zygomycetes. Studies of salvage therapy of zygomycosis with posaconazole have yielded promising results and there are additional case reports of successful outcomes using these and other antifungal drugs as combination therapy. Adjunctive approaches that are showing promise but with limited clinical experience are iron chelation and immunotherapy.