The Covid-19 pandemic has had a major impact on infants, children, and adolescents. While the clinical course of SARS-Cov2 is generally mild in young subjects, significant challenges in this age group have been identified regarding mental health. These challenges were associated with social distancing and public health measures employed to limit infection rates. Different countries chose to adopt different public health strategies concerning the extent of social isolation of children, for example, whether and how long schools were closed. Pandemic isolation as a natural experiment allows for assessing the consequences for the psychosocial development and mental health of the next generation. It has become clear that timely research is necessary to guide healthcare and welfare politics to provide adequate surveillance strategies for children and adolescents in order to make a maximum of safe social contact in this context possible. Moreover, the consequences of disease management measures such as social distancing, homeschooling, or mask-wearing for the well-being and mental health of the next generation also need to be quantified. The psychosocial burden on children and adolescents must be addressed and effective measures to return to healthy lives and learn our lesson for future pandemic situations need to be based on solid evidence. Apart from a dimensional assessment of sub-categorical impairments, clinical consequences with respect to categorical mood, anxiety, or eating disorders warrant a thorough examination. Adequate scientific instruments for the monitoring and assessment of psychosocial consequences for children and adolescents need to be provided, addressing both the view of parents and children and adolescents themselves. Finally, apart from safe real-life social contacts, digital technologies, and telemedicine interventions, ranging from videoconference-based psychotherapy to mobile phone apps, need to be further investigated in children and adolescents to provide adequate health care in a pandemic situation.