Development of chromatographic fingerprinting and its related chemometric methods in the research of quality control of traditional Chinese medicines (TCMs) are discussed. The quality control methods for guarantying the authentication and stability of products and semi-products of TCMs are firstly assessed. The technique based on chromatographic fingerprinting is essentially a kind of high-throughput and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs, confirmation and identification of their important chemical components are necessary. Some new strategies are proposed to trace the chemical changes of chromatographic fingerprints both in product processing and/or after their administration by modern chromatographic techniques and chemometrics. Combined with systems biology and bioinformatics, it seems possible for one to reveal the working mechanism of TCMs and to further control their intrinsic quality comprehensively.