Invasive fungal infections are a common problem in children affected by primary or secondary immunodeficiencies. Thanks to an increased knowledge about their mechanisms of action and their pharmacokinetic and toxicity profiles, the use of these drugs in common and uncommon invasive infections in immunocompromised children has improved over the last decades. Choosing the most appropriate antifungal drug is a serious challenge for any clinician, also considering that, in most cases, therapy has to be started before cultures are available, the choice being driven by clinical symptoms and statistical criteria only. In this study, we performed a systematic review of literature, providing antifungal treatment recommendations for paediatric patients which can help clinicians find the most suitable treatment for each specific case. Principal antifungal drugs-ranging from first-generation antimycotics to the latest molecules-are classified according to their targets, and of each group, the pharmacokinetic profile, clinical indications and side effects are extensively described.