Comprehensive two-dimensional gas chromatography (GC x GC) now occupies a niche within the GC technology regime. The technique is undeniably unique in the manner in which the experiment is conducted, the way results are presented and the interpretive opportunities offered. For the 1000th volume of this journal it is appropriate to expand upon these features, and review the progress made in GC x GC to date. Firstly, brief general comment is made on multidimensional procedures, and to review key aspects of GC x GC. The use of the targeted multidimensional GC method allows absolute retentions in the second dimension of a GC x GC experiment to be estimated, and also offers a novel way to obtain enhanced response for resolved solutes. Then, to illustrate the utility of the technique, the application of GC x GC to the screening of drugs and their metabolites in biological fluids is described using prolintane metabolites in canine urine as an example, with samples taken at four time intervals after administration. This example illustrates the first application of GC x GC in the field of forensic toxicology, an area traditionally dominated by GC-MS. Most drug compounds were found to be retained on the 0.8-m second column for a greater time than the modulation period (3 s) used for initial analysis, under the conditions described. Hence a 0.4-m D2 BPX50 (50% phenyl methyl polysilphenylene) column was then used throughout, with most compounds retained less than 4 s. For the standard drug mixture, three overlapping drugs on the first dimension column (BPX5) were subsequently baseline resolved on the BPX50 column. For prolintane administration samples, the parent drug and metabolites could be effectively resolved from background matrix peaks. Likewise a 23-drug spike standard in horse urine blank gave acceptable resolution of the drugs from matrix peaks.