The number of systemic fungal infection (SFI) cases is going due to the increase in immunocompromised hosts associated with advanced chemotherapy and high-tech medical devices. Aspergillus, Candida and Cryptococcus are major etiologies of SFIs and a remarkable increase of aspergillosis has been noted. The problems of SFIs in general are lower diagnostic rate and worse prognosis compared to infections by other pathogens. Clinical concerns of SFIs are the low diagnostic rate of aspergillosis, lack of evidence for treatment of chronic aspergillosis, poor outcome of cryptococcal encephalomeningitis of immunocompromised hosts, and increasing low azole-susceptible Candida. Our final goal is to overcome these problems and to develop a newer rapid diagnostic tool for aspergillosis, establish clinical trials for chronic aspergillosis, discover new pathogenic factors of Cryptococcus and evaluate alternative treatment for low azole susceptible Candida infections. We believe research advances in these areas will be useful in the diagnosing and treatment of SFIs in the future.