Transcutaneous carbon dioxide (CO2) analysis was introduced in the early 1980s using locally heated electrochemical sensors that were applied to the skin surface. This methodology provides a continuous noninvasive estimation of the arterial CO2 value and can be used for assessing adequacy of ventilation. The technique is now established and used routinely in clinical practice. Transcutaneous partial pressure of CO2 (tcPco2) sensors are available as a single Pco2 sensor, as a combined Pco2/Po2 sensor, and more recently, as a combined Pco2/Spo2 sensor. CO2 is still measured potentiometrically by determining the pH of an electrolyte layer. The methodology has been continuously developed during the last 20 yr, making the tcPco2 systems easier and more reliable for use in clinical practice: smaller sensor size (diameter 15 mm, height 8 mm), less frequent sensor re-membraning (every 2 wk) and calibration (twice a day), sensor ready to use when connected to the monitor, lower sensor temperature (42 degrees C), shorter arterialization time (3 min), and increased measurement reliability through protection of the membrane. The present tcPco2 sensors still need to be regularly re-membraned and calibrated. One way to overcome these procedures is to use optical-only detection means. Two techniques have been developed using optical absorption in the near-infrared light, in the evanescent wave of a waveguide integrated in the sensor surface, or in a micro-optics sampling cell. Preliminary in vitro and in vivo CO2 measurements have been performed. The sensor is not affected by drift over several days, and its response time is <1 min.