Pediatric healthcare system leaders are accustomed to being flexible and quickly shifting in response to dynamic healthcare trends. However, the COVID-19 pandemic brought an unprecedented onslaught of constant change, demanding leaders exercise great agility to meet the needs of patients, providers, and the communities they serve. In the early stages of the pandemic, fear of the unknown resulted in significant apprehension among patients and families. As a result, pediatric healthcare staff and providers became reliant upon swift communication and action from leaders to implement and adhere to organizational and public health guidelines. All aspects of pediatric healthcare delivery were impacted, requiring a multimodal response from leaders. This chapter will address implications of the COVID-19 pandemic for children’s health systems leaders and strategies used to address the challenges.