A health care system is needed where care is based on the best available evidence and is delivered reliably, efficiently, and less expensively (best care at lower cost). In gastroenterology, anti-tumor necrosis factor agents represent the most effective medical therapeutic option for patients with moderate-to-severe inflammatory bowel disease (IBD), but are very expensive and account for nearly a quarter of the cost of IBD care, representing a major area of present and future impact in direct health care costs. The ImproveCareNow Network, consisting of over 55 pediatric IBD centers, seeks ways to improve the value of care in IBD, curtailing unnecessary costs and promoting better health outcomes through systematic and incremental quality improvement initiatives. This report summarizes the key evidence to facilitate the cost-effective use of anti-tumor necrosis factor agents for patients with IBD. Our review outlines the scientific rationale for initiating cost-reducing measures in anti-tumor necrosis factor use and focuses on 3 implementable strategies and 4 exploratory considerations through practical clinical guidelines, as supported by existing evidence. Implementable strategies can be readily integrated into today's daily practice, whereas exploratory considerations can guide research to support future implementation.