Chemical fingerprinting is a structured analytical approach to identify and differentiate samples by analyzing their chemical profiles. These profiles can be generated using various techniques depending on the types of samples. Multi-component samples are typically analyzed using chromatographic methods, and advanced systems of two-dimensional gas chromatography (2D-GC) can be used to obtain chemical fingerprints of highly complex samples, such as petrochemicals or biologicals. The reliability of fingerprinting depends on experimental procedures and the ability to separate relevant compounds from the interferences. Without a well-optimized method, the results may be insufficient to detect differences, such as those found in adulterated food samples. Selecting suitable experimental conditions is thus essential to obtaining high-quality fingerprinting results. Since this often involves multiple experiments, the process can be time-consuming. However, applying experimental design techniques can reduce the number of experiments relying on predictive models of outcomes based on a limited dataset. This chapter discusses the core principles of chemical fingerprinting, the range of available analytical techniques, and the importance of experimental design in optimizing fingerprinting procedures.