Advances in medical therapy have allowed for increased survival of the most premature infants. These critically ill infants are immunocompromised and are often supported with invasive devices, placing them at risk for invasive candidiasis. Invasive candidiasis is associated with high mortality and significant comorbidities, including poor neurodevelopmental outcome. The changing epidemiology of invasive candidiasis, including an increasing prevalence of species resistant to traditional therapies, has mandated study of newer molecules. However, clinicians are hampered by a lack of randomized controlled trials of these molecules in premature infants. This chapter will describe the therapeutic options for prophylaxis and prevention, empiric therapy, and treatment of neonatal invasive candidiasis.