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, naturally occurring compounds and metals using different analytical techniques like inductively coupled plasma (ICP) sources, voltammetry and other techniques are provided in this Part. The use of experimental design techniques for optimization of extraction techniques is also emphasized. This survey will attempt to cover the state-of-the-art from 2004 to 2006.