The success rate of salvage therapy in invasive fungal infection is ~50%. These results have justified the use of combinations of antifungals to improve pharmacokinetic and pharmacodynamic performance and to avoid clinical antagonism. This review examines the sequence of introduction of antifungal agents as a means of avoiding this antagonism. It also analyses the possible inclusion of other drugs, such as calcineurin inhibitors or iron chelators, that can boost antifungal activity.