Publisher Summary This chapter discusses the advantages and limitations of the use of 2D gas chromatography (GCxGC) for the analysis of organic (semi-) volatile micropollutants in environmental matrices through selected applications that represent the current state-of-the-art in three main research fields: the analysis of organohalogenated pollutants, the determination of other nonhalogenated toxic compounds, and the enantiomeric analysis of chiral contaminants. GCxGC was rapidly incorporated in the analysis of organohalogenated compounds. Most of the research is carried out with alternative detectors—such as the flame ionization detector (FID) and the electron-capture detector (ECD)—in the early stage of development of the technique, with a clear preference for the micro-electron-capture detector (μECD) and time-of-flight mass spectrometry (ToF MS) in the past decade. A detailed study of the influence of the different experimental parameters affecting the modulation and acquisition data processes on the detectability and final identification of pesticides with GCxGC–ToF MS is presented in the chapter. The chapter also discusses the analysis of chiral pollutants in complex environmental samples.