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The incidence of invasive fungal infections has been on the rise, particularly in transplant recipients and in patients with hematological malignancies and other forms of immunosuppression. There is a mismatch between the rate of antifungal resistance and the development of new antifungal agents. Based on this, the idea of combining antifungals in the treatment of invasive fungal infections appears tempting for many clinicians, particularly after many in vitro studies showed synergism between many antifungal agents. Several randomized controlled trials have been published regarding the efficacy and safety of combination of antifungals, but the high cost, the limited number of cases and the multitude of confounding factors lead in some instances to weak and sometimes contradictory results. The lack of consensus in many clinical scenarios raises the importance of the need for more studies about combination antifungal therapies and should incite infectious disease societies to develop specific recommendations for the clinicians to follow while approaching patients with invasive fungal infections.