This chapter focuses on the effects of hypo- and hypercapnia at the organ and tissue level. Carbon dioxide's role in determining acid-base status and tissue oxygenation is described, followed by its effects on major organ systems. The higher lipid solubility of CO2 compared to hydrogen ions allows acid-base changes caused by respiratory acidosis and alkalosis to equilibrate between extra- and intracellular fluids much faster than changes caused by metabolic acidosis or alkalosis. The primary determinants of tissue oxygen availability are arterial O2 tension, cardiac output, and local perfusion. Hypocapnia induced by hyperventilation is clinically used for treatment of increased intracranial pressure (ICP), but the compromise in tissue perfusion, and thus the resulting secondary ischemia, should be factored into the risk-benefit equation. The active management of CO2 is a promising strategy to consider for improving tissue perfusion, providing anti-inflammatory effects, and preventing apoptotic injury.