Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the prescription of alkali for respiratory acidosis. We first describe the determinants of carbon dioxide retention in the 2 types of respiratory failure; hypercapnic respiratory failure and hypoxemic respiratory failure with coexisting hypercapnia. We then highlight the deleterious consequences of severe acidemia for several organ systems, particularly the cardiovascular and central nervous systems.