Preparative chromatography has been an integral component of pharmaceutical discovery and development for the past fifty plus years. The past thirty-five years have seen great advances in small molecule purification. Purification techniques have advanced from those centered around large irregular particles operating under low pressure to more efficient high-performance technologies utilizing small spherical particles. Technologies now routinely used include preparative HPLC, SMB, and SFC. At the discovery scale, these advances allow routine and rapid chiral and achiral purification of the large numbers of molecules synthesized at this stage of pharmaceutical R&D. For pharmaceutical development these advances allow chromatographic purifications using HPLC and SMB to be a standard tool in the process development toolbox. The large number of pharmaceutical chiral SMB operations at the manufacturing scale has shown that chromatography can be a cost-effective alternative to asymmetric synthesis or other resolution techniques.