Over the past decade, the incidence of hospital-acquired bloodstream infections caused by Candida species has risen and the species associated with such infections have changed. The incidence of candidemia is dramatically higher in high-risk, critical-care units than in other parts of the hospital. Certain underlying physical conditions including acute leukemia, leukopenia, burns, gastrointestinal disease, and premature birth predispose patients to nosocomial candidemia. Independent risk factors include prior treatment with multiple antibiotics, prior Hickman catheterization, isolation of Candida species from sites other than the blood, and prior hemodialysis. In this article some of the challenges posed by the management of nosocomial candidemia are presented in three case studies. In addition, the results of several investigations of nosocomial candidemia at the University of Iowa Hospitals and Clinics are reviewed.