Ion mobility spectrometry (IMS) has potential analytical applications in very diverse fields such as chemical, petrochemical, environmental, and, more recently, in drug, chemical warfare agent, and explosives detection. Commercially available IMS instruments are based on time-of-flight (TOF) mass spectrometry. IMS is inherently suitable for field operation as it uses relatively simple microfluidic devices and operates at atmospheric pressure. It is portable, highly sensitive with tunable selectivity, yet can be produced at relatively low cost. Key limitations of this analytical detection technique are low duty cycle, ion cluster formation, short linear dynamic range, and restriction to only positive or negative ion collection in a single analysis. Microelectromechanical system, radio frequency modulated IMS (MEMS RF-IMS), also known as differential mobility spectrometry, has recently been developed and commercialized. The technology is based on IMS, and MEMS RF-IMS offers substantially better performance. In this study, the strengths and limitations of the recently introduced differential mobility detector when used with gas chromatography in trace analyses are discussed and illustrated with applications of industrial significance.