Rapid sequence intubation (RSI) remains a cornerstone of airway management in critically ill patients, aiming to optimize oxygenation and ventilation, reduce the risk of secondary brain injury, and prevent gastric aspiration. Originally designed to minimize the interval between loss of airway reflexes and airway protection, while also limiting hemodynamic complications, RSI is now widely used in the operating room, intensive care unit, and emergency department. While aspiration prevention has historically been a central rationale for RSI, emerging evidence suggests that RSI may not significantly reduce this risk and may, in fact, be associated with increased rates of hypoxemia and hemodynamic instability. Pharmacological approaches, airway management techniques, and team-based preparation must be tailored to mitigate these complications. Contemporary RSI involves thorough preintubation assessment, preparation, and teamwork, emphasizing first-pass intubation success, patient positioning, apneic oxygenation, and gentle ventilation when appropriate. Several interventions have shown a clinically significant reduction of adverse events, such as the use of a video laryngoscope, apneic bag mask ventilation, or non-invasive ventilation for pre-oxygenation. The main recommended medications include a sedative (etomidate or ketamine are favored over propofol in hemodynamically unstable patients) and a paralytic (rocuronium or succinylcholine). Human factors, team-based preparation, and first-pass success remain key determinants of RSI outcomes. This narrative review synthesizes current evidence on RSI, highlighting pharmacological strategies, airway management techniques, and human factors, reflecting a shift from rigid protocols toward a more flexible, patient- and team-centered approach that balances aspiration risk with the prevention of desaturation and hypotension.