A review is presented on recent applications of experimental design and optimization techniques for the analysis of compounds of food, biomedical, toxicological and environmental concern. The main features and the significant advantages of chemometric approaches are discussed. Examples related to the determination of substances like xenobiotics or naturally occurring compounds using different analytical techniques, i.e. gas chromatography (GC), liquid chromatography (LC) and capillary electrophoresis (CE) are provided in this Part. The use of experimental design techniques for optimization of extraction techniques is emphasized as well as the importance of experimental design in checking robustness of analytical methods. This survey will attempt to cover the state-of-the-art from 2004 to 2006.