In early 2020, the world was overwhelmed by the novel respiratory coronavirus disease 2019 (COVID-19). Healthcare providers and researchers urgently explored traditional methods of pharmaceutical treatment, including anti-inflammatory, steroid, and antiviral medications routinely used to treat other known inflammatory respiratory diagnoses. However, novel and off-label prescribing of medications including antiviral, immunomodulator, and glucocorticoid therapy carries risks of adverse effects and necessitates careful consideration and close monitoring, especially in children. Other pharmacologic and complementary alternative approaches to treat COVID-19 are scarcely researched, particularly in pediatric populations. Stringent research requirements present both barriers and safeguards for prescriptive considerations for children. Holistic approaches to immune system support create opportunities for consideration that includes integration of preventive health measures.