Proton transfer reaction mass spectrometry (PTR-MS) is a relatively new analytical technique ideally suited for real-time measurement of a wide range of volatile organic compounds (VOCs). The VOCs may originate from any source, including groundwater release into the vadose zone, building vapor intrusion, and above ground vapor releases. Although PTR-MS has only been commercially available for approximately 15 years, the technology is based on the heavily studied and well-understood thermochemistry of ion–molecule reactions in the gas phase at moderate pressures of 2 mbar. Using H3O+ as a reagent ion, a proton transfers to compounds with a proton affinity greater than water, e.g., acetone, acetaldehyde, methanol, benzene, toluene, xylene, trichloroethylene, and many others present in soil gas or ambient air. For those volatile compounds not protonated by H3O+, such as vinyl chloride, tetrachloroethylene, or methane, NO+ or O2+ can be used. Water vapor flows into a hollow cathode where H+, H2+, OH+, and H2O+ are produced and then glide into a secondary drift tube reacting with H2O to produce H3O+. Interfering ions, such as NO+, O2+, and water clusters, are minimized by specifically tuning the ion source. The PTR-MS is ideal for trace gas measurements in air, as there are no reactions with the primary components of air, such as N2, O2, Ar, and CO2. No gas supply is necessary and the instrument is relatively small, requiring little maintenance and operating costs, allowing the instrument to be mounted in a van. Samples do not need to be prepared or pre-concentrated and there is no carrier gas. Air samples are introduced directly into the drift tube allowing for dynamic pore space sampling or VOC flux measurements. Long sampling lines can be used to transport the sample from the source to the instrument with no sensitivity loss. The instrument background ion signal is monitored periodically while acquiring real time data by delivering VOC free air to the instrument. The sensitivity is expressed in terms of the H3O+ count rate as normalized sensitivity (normalized counts per second). The H3O+ count rate varies throughout instrument operation as it depends on the age of the ion source, drift conditions, and applied detector voltage. For this reason, the normalized sensitivity is determined periodically during PTR-MS operation. The normalized counts per second are determined by normalizing the ion signal of a VOC in a calibration mixture (RH+cal) at a known mixing ratio (MRcal) to the reagent ion count rate expressed per million counts. A calibration blend of select VOCs in air or some permeation source gas is delivered to the instrument to calculate the normalized sensitivity and to calculate an ambient air or soil gas concentration of the VOC of interest. The sensitivity of the instrument allows the real-time measurement of VOC fluxes at mid- to low parts-per-trillion volume. The use of the mass spectrometer provides high specificity for monitoring specific compounds, while also delivering a wide dynamic range of operation.