Nanopore technology has been commercialised for the sequencing of DNA and RNA. It is a versatile approach and might also be used for the sensing of a wide variety of analytes, including small molecules. For example, humans release over 4000 volatile organic compounds (VOCs), which might be markers for the diagnosis of a variety of ailments. However, the analysis such a large number of analytes requires the application of expensive and bulky instrumentation, such as gas chromatography/ mass spectrometry. By using covalent nanopore sensing, we show that a reduced set of analytes, namely aldehydes, which constitute ~5 % of human volatiles, can be selectively detected. Our approach uses reversible thiol-aldehyde chemistry, in which aldehydes form hemithioacetals within the lumen of an engineered protein pore with lifetimes of tens of milliseconds. High resolution recording of transmembrane currents allows closely related aldehydes, even isomers, to be distinguished. Further, other classes of chemicals can be detected by conversion to aldehydes and alternative detection chemistries are available. The nanopore approach is inexpensive and can be housed in portable, user-friendly devices. As well as in the diagnosis of disease, such devices can be used for a wide variety of applications, including the detection of VOCs from pollutants and perishable foodstuffs.