Trimethylsilyl derivatives are routinely employed in gas chromatography to increase the volatility and stability of organic compounds containing active hydrogens. Normally only the desired derivative is formed when organic compounds are derivatized with common silylation reagents. However, some compounds form additional unexpected derivatives or by-products (artifacts). Artifact formation leads to multiple peaks for the same compound or unexpected components in the gas chromatographic analysis of mixtures. This review includes silylation artifacts identified in our laboratory by mass spectrometry during the last 20 years and references to those found in the literature. Also, means of avoiding artifact formation are discussed in detail.