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Outcomes in organ transplant recipients with invasive aspergillosis remain sufficiently dismal that combination antifungal approaches present an attractive therapeutic option. The efficacy of such approaches has not been incontrovertibly documented. However, limited data suggest that combination antifungal therapy may be considered in subsets of high-risk patients e.g. those renal and replacement therapy in whom mortality rates have typically exceeded 90%. Synergistic interactions of antifungal agents with the immunosuppressants suggest a role for devising antifungal strategies that target novel signalling pathways. Finally, manipulating known predisposing immunological defects with immunotherapeutic agents is a potentially promising approach for the management of these challenging opportunistic mycoses.