A team approach is optimal in the evaluation and treatment of musculoskeletal infection in pediatric patients given the complexity and uncertainty with which such infections manifest and progress, particularly among severely ill children. The team approach includes emergency medicine, pediatric intensive care, pediatric hospitalist medicine, infectious disease service, orthopaedic surgery, radiology, anesthesiology, pharmacology, and hematology. These services follow evidence-based clinical practice guidelines with integrated processes of care so that children and their families may benefit from data-driven continuous process improvement. Important principles based on our experience in the successful treatment of pediatric musculoskeletal infection include relevant information gathering, pattern recognition, determination of the severity of illness, institutional workflow management, closed-loop communication, patient and family-centered care, ongoing dialogue among key stakeholders within and outside the context of direct patient care, and periodic data review for programmatic improvement over time. Such principles may be useful in almost any setting, including rural communities and developing countries, with the understanding that the team composition, institutional capabilities or limitations, and specific approaches to treatment may differ substantially from one setting or team to another.