Emergency physicians intubate critically ill patients almost daily. Intubation of the critically ill emergency department (ED) patient is a high-risk, high-stress situation, as many have physiologic derangements such as hypotension, hypoxemia, acidosis, and right ventricular dysfunction that markedly increase the risk of peri-intubation cardiovascular collapse and cardiac arrest. This chapter discusses critical pearls and pitfalls to intubate the critically ill ED patient with physiologic derangements. These pearls and pitfalls include appropriate preoxygenation; circulatory resuscitation; proper patient position and room setup; selection of medications for rapid sequence intubation; and intubation of patients with severe acidosis, traumatic brain injury, and pulmonary hypertension.