Patients with respiratory failure should be approached in a systematic way, with emphasis both in diagnosis and treatment on arterial blood gases. The intelligent assessment of oxygenation, ventilation and acid-base balance, based on physiologic principles, can make the management of these patients very rewarding. The physiologic principles outlined here should be well understood by anyone entrusted with the care of these patients. They provide the cornerstone of diagnosis and management, and will remain valid long after current clinical dogma has been revised.