Children have unique physiologic, developmental, and psychosocial needs and unique vulnerabilities, making them a challenging population for which to develop therapeutics. This is particularly apparent in the urgent and chaotic environment of a pandemic or outbreak. Advances in the development of medical countermeasures (MCMs) for pediatric populations have grown substantially over the last decade, and the coronavirus disease 2019 pandemic forced advancements in how we approach pediatric MCM development. Consequently, a MCMs pipeline targeting the pediatric population is essential. This article addresses the challenges inherent in these differences that must be taken into account.