Treatment of fungal infections is an area of increasing concern. This is because of the complexity of underlying illness in affected patients as well as the limited number of antifungal agents available for use. Current strategies focus on prevention of these infections in patients at high risk; however, this has the potential to lead to the emergence of clinically resistant pathogens and superinfections in these patient populations. Future efforts need to focus on earlier diagnosis and more targeted prophylaxis strategies to limit unnecessary use of these potentially toxic pharmaceuticals. Of equal importance is the development of new therapeutic options that provide viable alternatives for practitioners as well as optimal administration of currently available agents. Recent work in this area has yielded a handful of new agents that provide the first step in improving efficacy in these severely immunosuppressed patients, but outcomes still remain suboptimal for many patients suffering from severe fungal infections and/or serious underlying diseases. Clinical antifungal drug resistance must be controlled by improving a series of antifungal therapeutic strategies.