As the incidence rates of neonatal systemic fungal infections (SFI) have been increasing over the last years, research efforts have been addressed towards identifying both effective preventative strategies, and efficacious and well-tolerated antifungal drugs. Historically, the first options in treatment of neonatal SFI have been – and currently are – fluconazole and amphotericin B. However, these two drugs carry limitations both in efficacy and in putative toxicity. Recently, new therapeutic alternatives have drawn the neonatologists' attention. Echinocandins are a new class of antifungal drugs with characteristics that might better meet the needs of this particular population of patients. Caspofungin (CSP), micafungin (MICA), and anidulafungin have inherent good activities both against biofilms, and against natively fluconazole-resistant strains of Candida spp, thus overcoming two of the major weaknesses of the commonly used antifungal drugs in nurseries. CSP and MICA have been recently studied in neonatal populations. The kinetics and appropriate dosing of this agent in premature and term infants have been described, but ongoing further studies are needed to better address this area. Case-report series show clinical efficacy and tolerability in critical neonatal patients given CSP and MICA. In addition, extrapolation of data from randomized trials conducted in pediatric and adult patients showed through a subgroup analysis that both CSP and MICA are effective and well tolerated also in neonates. Further studies properly designed for neonatal populations will better address long-term safety and ecological issues related to echinocandin use in neonates.