Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children generally have milder presentations, but severe disease can occur in all ages. MIS-C and persistent post-acute COVID-19 symptoms can be experienced by children with previous infection and emphasize the need for infection prevention. Optimal treatment for COVID-19 is not known, and clinical trials should include children to guide therapy. Vaccines are the best tool at preventing infection and severe outcomes of COVID-19. Children suffered disproportionately during the pandemic not only from SARS-CoV-2 infection but because of disruptions to daily life, access to primary care, and worsening income inequalities.