Abstract Aspiration of gastric contents during induction of general anesthesia remains a significant cause of mortality and morbidity in anesthesia. Recent data show that pulmonary aspiration still accounts for many cases with implications on mortality despite technical and technological evolution. Practical, ethical, and methodological issues prevent high-quality research in the setting of aspiration and rapid sequence induction/intubation, and significant controversy is ongoing. Patients’ position, drugs choice, dosing and timing, use of cricoid force, and a reliable risk assessment are widely debated with significant questions still unanswered. We focus our discussion on three approaches to promote a better understanding of rapid sequence induction/intubation and airway management decision-making. Firstly, we review how we can use qualitative and quantitative assessment of fasting status and gastric content with the point-of-care ultrasound as an integral part of preoperative evaluation and planning. Secondly, we propose using imaging-based mathematical models to study different patient positions and aspiration mechanisms, including identifying aspiration triggers. Thirdly, we promote the development of a global data collection system aiming to obtain precise epidemiological data. Therefore, we fill the gap between evidence-based medicine and experts’ opinion through easily accessible and diffused computer-based databases. A better understanding of aspiration epidemiology obtained through focused global data gathering systems, the widespread use of ultrasound-based prandial status evaluation, and development of advanced mathematical models might potentially guide safer airway management decision making in the 21st century.