Children are unique in the context of the COVID-19 pandemic. Overall, SARS-CoV-2 has a lower medical impact in children as compared to adults. A higher proportion of children than adults remain asymptomatic following SARS-CoV-2 infection and severe disease and death are also less common. This relative resistance contrasts with the high susceptibility of children to other respiratory tract infections. The mechanisms involved remain incompletely understood but could include the rapid development of a robust innate immune response. On the other hand, children develop a unique and severe complication, named multisystem inflammatory syndrome in children, several weeks after the onset of symptoms. Although children play an important role in the transmission of many pathogens, their contribution to the transmission of SARS-CoV-2 appears lower than that of adults. These unique aspects of COVID-19 in children must be considered in the benefit–risk analysis of vaccination. Several COVID-19 vaccines have been authorized for emergency use in adolescents and clinical studies are ongoing in children. As the vaccination of adolescents is rolled out in several countries, we shall learn about the impact of this strategy on the health of children and on transmission within communities.