Fungal-related morbidity and mortality is a major concern for most neonatal intensive care units (NICUs) worldwide. Incidence rates are increasing and might be higher than reported due to the challenges associated with diagnosing fungal infections. As preterm neonates display clinical characteristics that make them prone to Candida spp infections, and there is a high frequency of severe neurodevelopmental sequelae in those who survive neonatal fungal infections, specific prevention--rather than empiric or pre-emptive treatment--should be the optimal strategy. Besides stewardship of drug use and efforts to minimize invasive cares, pharmacological prevention with use of fluconazole has proved highly effective in decreasing the rates of fungal sepsis in very low birth weight (VLBW) neonates. Alternative options needing further and more conclusive assessments include use of nystatin, bovine lactoferrin or probiotics.