Approximately 3 million critically ill patients are intubated and initiated on mechanical ventilation each year in the United States. A critical component of mechanical ventilation is the adjustment of FiO2 to maintain adequate arterial oxygen saturation.  However, the optimal oxygenation target in critically ill adult patients receiving mechanical ventilation remains uncertain. In this podcast we discuss a recently published study, the PILOT Trial, that evaluated low, intermediate, and high oxygenation targets in critically ill patients.