Invasive fungal infection is an important cause of mortality and morbidity in very low birthweight (VLBW) infants. Extremely preterm and extremely low birthweight infants are at highest risk because of the intensive and invasive nature of the care that these infants receive. Additional specific risk factors include prolonged use of parenteral nutrition and exposure to broad-spectrum antibiotics and histamine type 2 receptor blockers. Diagnosis is difficult and often delayed, and this may contribute to the high levels of deep-organ dissemination and associated mortality and morbidity. The most commonly used antifungal agents are amphotericin B and fluconazole. Recent research has assessed the value of early empirical and prophylactic treatment. However, although systemic antifungal prophylaxis reduces the incidence of invasive fungal infection, there is no evidence of effect on mortality. Concern exists about the impact that widespread use of prophylaxis may have on the emergence of antifungal resistance.