OBJECTIVE Fungal infections are prevalent in very low birthweight (<1500 g) infants and are associated with significant morbidity and mortality. A better understanding of the adherence factors, molecular diagnostics and risk factors for invasive fungal infection are important in treatment and prevention. RESULTS Animal studies have demonstrated that Candida readily adheres to apical microvilli and the junctions between enterocytes. Although antibiotics facilitate colonization, dissemination occurs with immunosuppression. The INT1 gene is associated with enhanced colonization and dissemination in these animal models. Dissemination is probably caused by yeast cell adherence and invasion, whereas tissue injury may be related to filamentous formation. Polymerase chain reaction techniques have demonstrated promise in neonatal patients and may not only detect bloodstream infection, but fungal infection at other sites. At the time of fungal sepsis, less than 28 weeks' gestation, thrombocytopenia, and previous exposure to broad-spectrum antibiotics continue to be risk factors for infection. Empiric therapy is still being defined and investigated. Fluconazole prophylaxis should be strongly considered in the most immature infants. CONCLUSIONS Preventative strategies against fungal colonization and infection are critical in high-risk very low birthweight infants. Also promising is the ability of molecular diagnostics to detect infection earlier, allowing for prompt treatment, including central venous catheter removal. Identifying the highest risk very low birthweight infants for prophylaxis and empiric therapy may lead to better outcomes. Multicenter clinical trials of fluconazole prophylaxis to confirm its safety and efficacy, and of empiric treatment to test safety and outcomes are urgently needed.