A portable tandem mass spectrometer, capable of performing atmospheric pressure chemical ionization (APCI) using a direct atmospheric inlet, is applied to the real-time monitoring of toxic compounds in air. Analytes of interest include dimethyl methylphosphonate, arsine, benzene, toluene, pyridine and vinyl acetate. The detection, identification and quantification of organic and inorganic compounds in air is demonstrated using short analysis times (<5 seconds) with detection limits in the low ppb (v/v) levels and linear dynamic ranges of several orders of magnitude. Highly specific detection and identification is achieved, even when the analyte is a trace component in a complex mixture including such interferents as fuels, lubricants, and cleaners. The effects of environmental conditions, including temperature and humidity, are delineated. Receiver operating characteristic (ROC) curves are presented to show the trade-off between false positive and false negative detection rates. Tandem mass spectrometry based both on collision-induced dissociation and on selective atmospheric pressure ion/molecule reactions is also used to increase selectivity and sensitivity.