Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.