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The monitoring of partial pressures of the blood gases carbon dioxide (pCO2) and oxygen (pO2) is of great importance in clinical diagnostics. The measure of pCO2 and pO2 provides essential information about the patient’s metabolism, gas exchange, ventilation, and acid–base homeostasis. The conventional electrochemical methods for clinical blood gas analysis are based on the potentiometric Severinghaus sensor for carbon dioxide and the amperometric Clark sensor for oxygen. These techniques are well established and are only shortly discussed in this overview. However, in recent years a variety of modifications of these classical sensor concepts and new approaches of electrochemical sensing of pCO2 and pO2 have been introduced. This review summarizes recent developments in this field and discusses the potential for future applications in clinical blood gas analysis.