Background: Infectious diseases are a leading cause of morbidity and mortality worldwide. As of 2018, the total world population of children < 5 years of age was roughly estimated at 679 million. Of these children, an estimated 5.3 million died of all causes in 2018, with an estimated 700,000 who died of vaccine-preventable infectious diseases; 99% of the children who died had lived in low- and middle-income countries. The infectious diseases that remain major causes of mortality for which vaccines have been shown to provide proven preventive success include, in order of prevalence, are those caused by Streptococcus pneumoniae, Rotavirus, Bordetella pertussis, measles virus, Haemophilus influenzae type b and influenza virus. Objective: The purpose of the present report was to address the global burden of these six vaccine-preventable infectious diseases in children < 5 years of age, together with implications for the prevention of coronavirus disease 2019 (COVID-19) infection in children. Methods: The current immunization strategies for the prevention of the six vaccine-preventable infectious diseases in children are reviewed as a framework for new strategies of vaccine prevention of COVID-19 in children. Results: The burden of addressing vaccine prevention of future infectious disease in children can be effectively pursued through knowledge gained from past experiences with vaccine usage in these six vaccine-preventable childhood infectious diseases. Conclusion: Issues with regard to the burden of disease mortality, disease transmission, and available vaccines as well as vaccine successes and shortcomings for specific pathogens can serve as important landmarks for effective use of future vaccines. Although much success has been made globally in preventing these childhood deaths, much remains to be done.