Carbon dioxide is a waste product of aerobic cellular respiration in all aerobic life forms. PaCO2 represents the balance between the carbon dioxide produced and that eliminated. Hypocapnia remains a common - and generally underappreciated - component of many disease states, including early asthma, high-altitude pulmonary edema, and acute lung injury. Induction of hypocapnia remains a common, if controversial, practice in both adults and children with acute brain injury. In contrast, hypercapnia has traditionally been avoided in order to keep parameters normal. More recently, advances in our understanding of the role of excessive tidal volume has prompted clinicians to use ventilation strategies that result in hypercapnia. Consequently, hypercapnia has become increasingly prevalent in the critically ill patient. Hypercapnia may play a beneficial role in the pathogenesis of inflammation and tissue injury, but may hinder the host response to sepsis and reduce repair. In contrast, hypocapnia may be a pathogenic entity in the setting of critical illness. The present paper reviews the current clinical status of low and high PaCO2 in the critically ill patient, discusses the insights gained to date from studies of carbon dioxide, identifies key concerns regarding hypocapnia and hypercapnia, and considers the potential clinical implications for the management of patients with acute lung injury.