Hypoxemia is an abnormally low concentration of oxygen in the blood which can lead to dire consequences when left unmanaged. In most patients with hypoxemia, the application of supplemental oxygen is a quick bandaid therapy that is often applied to counteract the problem. However, have you ever applied supplemental oxygen to a patient experiencing hypoxemia and there has been a minimal effect? Have you ever wondered why the application of supplemental oxygen works in some patients but not others? It all comes down to what is causing the hypoxemia and understanding the pathophysiology behind a ventilation/perfusion (VQ) mismatch.