The effect of using self-assembled monolayers to facilitate the physical and chemical adsorption of analytes onto surface-enhanced infrared absorption (SEIRA) gold substrates has been investigated. Self-assembled monolayers of thiopropane, thiohexane, and thiophenol were tested to determine the response for short and medium-size normal alkanes monolayers and aromatic monolayers. The analytes consisted of 4,6-difluro-nitrobenzene, o-dinitrobenzene, 4,6-dinitro-o-cresol, and tri-nitrobenzene. Spectral results for the self-assembled monolayers were compared to those obtained with an uncoated gold SEIRA surface and with typical transmission spectra of the same test samples. Some enhancement was obtained in all cases; however, the aromatic thiol monolayer produced the largest enhancements, with a maximum increase of 21 fold. As a practical application of the SEIRA technique, a prototype sensor for the detection of trinitrotoluene (TNT) was prepared and tested.