Selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry with switchable reagent ion capability (PTR+SRI-MS) are analytical techniques for real-time qualification and quantification of compounds in gas samples with trace level concentrations. In the detection process, neutral compounds-mainly volatile organic compounds-are ionized via chemical ionization with ionic reagents or primary ions. The most common reagent ions are H3 O+ , NO+ and O2 +• . While ionization with H3 O+ occurs by means of proton transfer, the ionization via NO+ and O2 +• offers a larger variety on ionization pathways, as charge transfer, hydride abstraction and so on are possible. The distribution of the reactant into various reaction channels depends not only on the usage of either NO+ or O2 +• , but also on the class of analyte compounds. Furthermore, the choice of the reaction conditions as well as the choice of either SIFT-MS or PTR+SRI-MS might have a large impact on the resulting products. Therefore, an overview of both NO+ and O2 +• as reagent ions is given, showing differences between SIFT-MS and PTR+SRI-MS as used analytical methods revealing the potential how the knowledge obtained with H3 O+ for different classes of compounds can be extended with the usage of NO+ and O2 +• .