Central nervous system involvement in neonatal candidiasis is not rare, although possibly less frequent than in previous decades. In addition to increasing the potential for neurodevelopmental morbidity, this infection poses major challenges in establishing diagnosis and assuring adequate treatment. In the setting of candidemia or other severe invasive candida disease, suggestive imaging studies or inflammatory changes in cerebrospinal fluid should prompt careful consideration of central nervous system candidiasis even if culture of the fluid is negative. Although delivery of amphotericin to cerebrospinal fluid appears much better in premature infants than in older individuals, the availability of other agents with superior delivery to the central nervous system suggests that strong consideration be given to their use as alternative or adjunct therapy if central nervous system involvement appears likely. Careful surveillance for neurodevelopmental sequelae may permit early detection, timely rehabilitative intervention, and potentially better long-term functional outcomes.