Drug shortages have become increasingly common in recent years, especially in the United States. Some pediatric chemotherapeutics have frequently been in short supply, posing serious risks to patient safety. This commentary describes an ethical framework developed by a multidisciplinary group of experts and a panel of peer consultants. The framework seeks to guide clinicians' decision-making around allocating life-saving chemotherapies and associated drugs for children with cancer. The authors describe methods for managing shortages by reducing waste. The guideline also provides clear reasoning for actual prioritization across and within common pediatric cancers during a drug shortage. For example, in cases where shortages lead to the inability to provide the standard of care for some children, the authors propose emphasizing curability and prognosis in determining who is likely to have the most benefit. In 2013, the FDA released a strategic plan for preventing drug shortages, but the problem has continued largely unabated.