Neonates represent a unique and highly vulnerable patient population. Advances in medical technology have improved the survival and quality of life of newborns, particularly those with extreme prematurity or with congenital defects. Furthermore, immunologic immaturity and altered cutaneous barriers play some role in the vulnerability of neonates to nosocomial infections. In this context, the incidence of invasive fungal infections has increased significantly worldwide, representing an important infective complication in patients hospitalized in intensive care units. Invasive fungal infections in Neonatal Intensive Care Unit (NICUs) show high mortality; being species of Candida, the most isolates etiologic agents. The better prognosis of the patient is associated with the early diagnosis and fast treatment. However, guidelines to facilitate the optimal therapy choice for the treatment of neonatal fungal disease do not exist. The current antifungal agents that are available to treat fungemia among newborns and children are based on clinical trials in adults, since there are few comparative studies of antifungal agents in infants. The most commonly used drugs for the treatment of invasive fungal infections in neonates are classified in four different classes: polyene, azoles, analogs of pyrimidines and echinocandins.