Children’s hospitals represent a significant opportunity to reduce morbidity, mortality, and costs, particularly for children with complex chronic conditions (CCCs) who comprise a disproportionate and growing share of admissions, readmissions, and resource use. Most children with CCCs are in some way associated with a children’s hospital, and the subspecialists who care for them are primarily concentrated in the ∼200 children’s hospitals in the United States. Children’s hospitals and their associated subspecialty clinics are uniquely positioned to achieve significant outcomes and cost savings through coordinated quality-improvement efforts. However, even the largest children’s hospital has relatively small volumes of patients with any given condition. Only by linking children’s hospitals in networks can a sufficient “N” be achieved to build the evidence for what works for children. Large-scale pediatric collaborative network exemplars have demonstrated the ability to improve outcomes, reduce costs, and spread changes found to be effective. Substantial opportunities exist for networks to expand to additional conditions, improvement topics, and sites, but financial barriers exist. Although much of their participation has been funded as “pay to participate” efforts by the hospitals themselves, most financial benefits accrue to payers. As health care reform becomes a reality and financial pressures intensify, it will become increasingly difficult for children’s hospitals to serve as the primary source of support for networks. Partnerships between children’s hospitals and national payers to support collaborative networks are needed, and these partnerships have the potential to significantly improve pediatric care and outcomes, particularly for children with CCCs.