A black box warning, also known as a boxed warning, represents the most serious type of safety alert that the U.S. Food and Drug Administration can require for prescription drug labeling. The name derives from the distinctive black border that surrounds the warning text, drawing immediate attention to critical safety information. These warnings are reserved for risks that are serious enough to warrant special emphasis and typically involve risks of death or severe, potentially irreversible adverse effects that may affect prescribing decisions or require special monitoring.

The FDA may require a black box warning when evidence demonstrates a serious risk that prescribers should be aware of when making treatment decisions. This evidence may emerge during clinical development, leading to the warning being included in the initial approved labeling, or may surface during post-marketing surveillance, necessitating labeling updates for products already on the market. In either case, the warning must describe the nature and magnitude of the risk, the affected population, and any recommended monitoring or precautions.

While black box warnings are specific to FDA-regulated products in the United States, similar concepts exist in other regulatory jurisdictions. The European Medicines Agency may require prominent safety warnings, and products may carry restrictions on their use through risk evaluation and mitigation strategies. For clinical trials conducted under FDA jurisdiction, the presence of black box warnings on comparator drugs or the anticipation of such warnings for investigational products influences protocol design, informed consent content, and safety monitoring requirements throughout development.