The burden of COVID-19 is significantly lower in children as compared to adults, and their role in the transmission of the diseases seems to be less relevant than in other respiratory infections. For these reasons, the development of the vaccines targeting the adult population was the first priority. Now we have learnt vaccines are safe and efficacious in adult populations, down-age de-escalation trials will be performed. Children are a unique population with distinct developmental and physiological differences from adults. Clinical trials in children are essential to develop age-specific, empirically-verified therapies and interventions to determine and improve the best medical treatment available. However, children are an exceptional population about which there are specific ethical and clinical concerns. The vulnerable nature of this population must be considered when balancing the risks of research with the need for safe and validated therapies.