Persistent shortcomings of invasive positive pressure ventilation make it less than an ideal intervention. Over the course of more than seven decades, clinical experience and scientific investigation have helped define its range of hazards and limitations. Apart from compromised airway clearance and lower airway contamination imposed by endotracheal intubation, the primary hazards inherent to positive pressure ventilation may be considered in three broad categories: hemodynamic impairment, potential for ventilation-induced lung injury, and impairment of the respiratory muscle pump. To optimize care delivery, it is crucial for monitoring and machine outputs to integrate information with the potential to impact the underlying requirements of the patient and/or responses of the cardiopulmonary system to ventilatory interventions. Trending analysis, timely interventions, and closer communication with the caregiver would limit adverse clinical trajectories. Judging from the rapid progress of recent years, we are encouraged to think that insights from physiologic research and emerging technological capability may eventually address important aspects of current deficiencies.