Azithromycin mass drug administration (MDA) can reduce under-5 mortality in stable but high-mortality settings, yet its potential in humanitarian crises remains undefined. This review proposes that azithromycin MDA could support existing humanitarian interventions and help address mortality from respiratory and gastrointestinal infections in displaced populations. Mortality rates in crises frequently exceed WHO recommended thresholds for initiating MDA. Operationally, the MDA is feasible, low-cost, and synergises with existing relief efforts like vaccination. While antimicrobial resistance (AMR) is a serious concern, the proposed use, likely a single round or short-term intervention during acute emergencies, may mitigate long-term resistance selection compared to routine biannual dosing. The potential to rapidly reduce excess mortality may outweigh the AMR risks. Azithromycin MDA represents a promising new tool for humanitarian health, though evidence-based protocols and resistance monitoring strategies must be developed through further research.