Appeals for health equity call for departments of pediatrics to improve the health of all children including those from underserved communities in North America and around the world. Consequently, North American (NA) departments of pediatrics have a role in global child health (GCH) which focuses on providing health care to underserved children worldwide. In this review, we describe how NA departments of pediatrics can collaboratively engage in GCH education, clinical practice, research, and advocacy and summarize best practices, challenges, and next steps for engaging in GCH in each of these areas. For GCH in low- and middle-income countries (LMICs), best practices start with the establishment of ethical, equitable, and collaborative partnerships with LMIC communities, organizations, and institutions engaged in GCH who are responsible for the vast majority of work done in GCH. Other best practices include adequate preparation of trainees and clinicians for GCH experiences; alignment with local clinical and research priorities; contributions to local professional development and ongoing monitoring and evaluation. Challenges for departments include generating funding for GCH activities; recruitment and retention of GCH-focused faculty members; and challenges meeting best practices, particularly adequate preparation of trainees and clinicians and ensuring mutual benefit and reciprocity in NA-LMIC collaborations. We provide examples of how departments have overcome these challenges and suggest next steps for development of the role of NA departments of pediatrics in GCH. Collaborative implementation of best practices in GCH by LMIC-NA partnerships can contribute to reductions of child mortality and morbidity globally.