In this review, the role of secondary antifungal prophylaxis (SAP) in prevention of invasive fungal infections (IFIs) in patients with leukemia and in those receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) is discussed. A history of IFI is not an absolute contraindication for allo-HSCT or continuation of cytotoxic chemotherapy, provided that SAP is administered. We suggest that the last antifungal drug successfully used for treatment of the previous IFI is also used for SAP; during SAP, we propose an algorithm of thorough clinical, radiological and microbiological monitoring with monthly CT scan and twice weekly galactomannan assays. However, the optimal preventive strategy for patients with a prior IFI has not been defined and concerted efforts are warranted to optimize the management of affected patients.