BACKGROUND: Antibiotics have been among the drugs most affected by shortages over the last two decades, with harmful consequences that may persist over years. This position paper was designed by the Alliance for the Prudent Use of Antibiotics (APUA), an international multidisciplinary consortium of experts dedicated to combating antimicrobial resistance. METHODS: We performed a narrative review to examine the main causes and impacts of antibiotics shortages, and to identify the solutions that may be proposed to prevent and mitigate this public health threat. RESULTS: The main causes of antibiotic shortages are failure to comply with good manufacturing practices, regulatory issues, unavailability of essential components, unanticipated discontinuation of production by a major supplier, unexpected surges in demand, and other logistical challenges. The main consequences include delays in appropriate treatment administration, overuse of broad-spectrum antibiotics with an increased risk of resistance, reduced efficacy, and increased toxicity due to sub-optimal antibiotics use, increased costs, medication errors, and prolonged or repeated hospital stays. Proposed potential solutions for antibiotic shortages include multidisciplinary international initiatives to foster market entry rewards, specific solutions for low-and-middle income countries (LMICs), strengthening supply chains, encouraging local production, implementing market entry incentives and facilitating the registration process for novel antibiotics and vaccines. CONCLUSIONS: Antibiotics shortage severely impacts patient care and public health worldwide. The sustainability of both current and future antibiotics depends on the implementation of effective global health strategies and ongoing financial commitment. Immediate and decisive action is necessary to protect global health for future generations.