In the field of respiratory clinical practice, the importance of measuring carbon dioxide (CO₂) concentrations cannot be overemphasized. Within the body, assessment of the arterial partial pressure of CO₂ (PaCO₂) has been the gold standard for many decades. Non-invasive assessments are usually predicated on the measurement of CO₂ concentrations in the air, usually using an infrared analyzer, and these data are clearly important regarding climate changes as well as regulations of air quality in buildings to ascertain adequate ventilation. Measurements of CO₂ production with oxygen consumption yield important indices such as the respiratory quotient and estimates of energy expenditure, which may be used for further investigation in the various fields of metabolism, obesity, sleep disorders, and lifestyle-related issues. Measures of PaCO₂ are nowadays performed using the Severinghaus electrode in arterial blood or in arterialized capillary blood, while the same electrode system has been modified to enable relatively accurate non-invasive monitoring of the transcutaneous partial pressure of CO₂ (PtcCO₂). PtcCO₂ monitoring during sleep can be helpful for evaluating sleep apnea syndrome, particularly in children. End-tidal PCO₂ is inferior to PtcCO₂ as far as accuracy, but it provides breath-by-breath estimates of respiratory gas exchange, while PtcCO₂ reflects temporal trends in alveolar ventilation. The frequency of monitoring end-tidal PCO₂ has markedly increased in light of its multiple applications (e.g., verify endotracheal intubation, anesthesia or mechanical ventilation, exercise testing, respiratory patterning during sleep, etc.).