The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children was released in 2020 and is intended for use in all global settings that care for children with sepsis. However, practitioners managing children with sep sis in resource-limited settings (RLS) face several challenges and disease patterns not experienced by those in resource-rich settings. Based upon our collective experience from RLS, we aimed to reflect on the difficulties of implementing the international guidelines. We believe there is an urgent need for more evidence from RLS on feasible, efficacious approaches to the management of sepsis and septic shock that could be included in future context-specific guidelines.