Preparative chromatography (Prep) is a unit operation that is underutilized for the purification of active pharmaceutical ingredients. This technique is over 100 years old, and significant improvement has occurred in the past 20 years that makes this technology a very efficient and cost-effective process for either product purification or chiral separations. The author discusses the different modes of chromatography for large-scale separations (Batch, bio, SFC, SMB) and presents strategies for the development of a process in the perspective of commercial-scale manufacturing. The chapter also provides a review of the equipment available for the separation as well as the downstream processing. Finally, the Prep at commercial scale is discussed with an overview of the continuous chromatography process including regulatory aspects, manufacturing point of view, and economic perspectives.