Respiratory alkalosis is the most frequent acid-base disturbance encountered in clinical practice. This is particularly true in critically ill patients, for whom the degree of hypocapnia directly correlates with adverse outcomes. Although this acid-base disturbance often is considered benign, evidence suggests that the alkalemia of primary hypocapnia can cause clinically significant decreases in tissue oxygen delivery. Mild respiratory alkalosis often serves as a marker of an underlying disease and may not require therapeutic intervention. In contrast, severe respiratory alkalosis should be approached with a sense of urgency and be aggressively corrected.