AbstractAlthough comprehensive two‐dimensional gas chromatography (GC × GC) has been on the scene for more than 15 years, it is still generally considered a relatively novel technique and is yet far from being fully established. The revolutionary aspect of GC × GC, with respect to classical multidimensional chromatography, is that the entire sample is subjected to two distinct analytical separations. The resulting enhanced separating capacity makes this approach a prime choice when GC analysts are challenged with highly complex mixtures. The combination of a third mass spectrometric dimension to a GC × GC system generates the most powerful analytical tool today for volatile and semi‐volatile analytes. The present review is focused on the rather brief, but not scant, history of comprehensive two‐dimensional GC‐MS: the first experiments were carried out at the end of the 1990s and, since then, the methodology has been increasingly studied and applied. Almost all GC × GC‐MS applications have been carried out by using either a time‐of‐flight or quadrupole mass analyzer; significant experiments relative to a variety of research fields, as well as advantages and disadvantages of the MS systems employed, are discussed. The principles, practical and theoretical aspects, and the most significant developments of GC × GC are also described. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27:101–124, 2008