The incidence of invasive aspergillosis (IA) has dramatically increased over the last 20 years, especially among patients with hematological malignancies and organ transplant recipients [1,2]. IA is also being recognized more frequently in emerging populations such as in patients taking corticosteroids, in those with chronic obstructive pulmonary diseases, and in those receiving therapy with monoclonal antibodies [3,4]. Mortality rates from IA remain high as the underlying conditions predisposing to IA – particularly neutropenia – frequently cannot be reversed [5]. Due to the difficulties in diagnosing IA, many patients do not benefit from early therapy with antifungal drugs. Fortunately, in the last few years, newer diagnostic and therapeutic strategies have been incorporated into clinical practice. The purpose of this article is to critically review all randomized clinical trials with antifungal drugs. Trials were identified using a structured search strategy, as described below.