Proton-transfer reaction mass spectrometry (PTR-MS) allows for real-time, on-line determination of absolute concentrations of volatile organic compounds (VOCs) with a high sensitivity and low detection limits (in the pptv range). The technique utilizes H₃O⁺ ions for proton-transfer reactions with many common VOCs while having little to no reaction with any constituents commonly present in air. Over the past decades, research has greatly improved the applications and instrumental design of PTR-MS. In this article, we give an overview of the development of PTR-MS in recent years and its application in medical research. The theory of PTR-MS and various methods for discriminating isobaric VOCs are also described. We also show several specialized designs of sample inlet system, some of those may make PTR-MS suitable for the detection of aqueous solution and/or non-volatile samples.