This tutorial review charts the development of electrochemical sensors for the analysis of blood-gases, gases and vapours in clinical medicine over the past four decades. The development of each sensor is set in its historical and clinical context, and the first part of the review concentrates on aqueous electrolyte electrochemistry and on those sensors which have made a major impact on the clinical measurement of the partial pressures of oxygen and carbon dioxide in the blood. The electrochemical interference effects of anaesthetic agents on these measurements are also described. Those electrochemical sensors which have failed, in the past, to make a clear impact in this area are not considered, but the few attempts to devise aqueous electrolyte electrochemical sensors for anaesthetic agent measurement are reviewed. The second part of the review describes the chequered history of the development of non-aqueous solvent electrochemical sensors to measure the partial pressures of oxygen and carbon dioxide, in both the presence and absence of each other, in the gas phase. The last part of the review examines various attempts, using non-aqueous solvent electrochemistry, to measure the concentration of inhalational anaesthetic vapours in the gas phase. These sensors have yet to make an impact on clinical practice. Throughout this tutorial review, theoretical models of membrane-covered electrochemical sensors are described where appropriate. This review represents a personal view of the development of electrochemical sensors for clinical measurement, and it is therefore necessarily selective in its approach and emphasis.