Preparative chromatography is the best generic method currently available for purifying small drugs and valuable chemical components at the 10-kg level. Progress in computer technology, the development of new non-chiral/chiral stationary phases, and numerous improvements in reliability and economic performance have considerably increased the interest in modeling in academia and industry. This chapter introduces the modeling of preparative liquid chromatography in order to improve the purification process for valuable chemical components such as drugs and chiral components. We review the most important column and adsorption models and the methods for determining the essential thermodynamic adsorption data for both column characterization and process improvement. We also cover important operational modes (e.g., separation in gradient mode), cases involving additives or ion-pair reagents, and operational conditions sometimes neglected in the modeling process, for example, involving the impact of injection profiles.