Invasive fungal infections are important causes of morbidity and mortality in patients with bone marrow failure syndromes and hematological malignancies, or who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Current epidemiological trends indicate a shift toward infections by Aspergillus spp., non-albicans Candida spp., and previously uncommon fungal pathogens that have decreased susceptibility to the available antifungal agents. The last two decades have seen substantial improvements in the clinical, laboratory, and radiological diagnosis of these infections and the development of new antifungal compounds. Progress has been made in establishing disease definitions and paradigms for antifungal intervention and in the design and conduct of interventional clinical trials. Collectively, these advances have led to major but ongoing changes in the management of patients at risk of or being affected by invasive fungal infections. This article reviews current approaches to prevention and treatment of opportunistic fungal infections in immunocompromised patients with hematological disorders and discusses novel approaches to antifungal chemotherapy and adjunctive treatments.