INTRODUCTION: Invasive fungal infections (IFIs) in neonatal and pediatric patients are still associated with high morbidity and mortality, increased length of hospital stay and high healthcare cost. Two key components are prerequisite to combat pediatric IFIs; first, definition of the 'at-risk' populations that could benefit the most from prophylactic treatment and second, prompt initiation of effective antifungal therapy.AREAS COVERED: In this article, updated prevention and targeted therapeutic approaches for IFIs in neonates and immunocompromised children are reviewed. Furthermore, European and American guidelines concerning IFI treatment in neonates and children are compared.EXPERT OPINION: IFIs in neonates and children present substantial differences from adults in respect to their epidemiology, pharmacokinetics of antifungal agents and dosing as well as absence of interventional Phase III and IV clinical trials for guidance of evidence-based decisions. In the therapeutic armamentarium of these age groups, although amphotericin B formulations remain widely indicated, azoles with broader spectrum activity as well as echinocandins have been added in the updated antifungal treatment algorithm. Recent European guidelines (ESCMID and ECIL) contain specific recommendations for pediatric patients with IFIs. In both age groups, definitive updated guidance for prophylaxis and more importantly targeted treatment need to be further evaluated by large, multicenter, randomized controlled trials.