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Publisher Summary This chapter discusses the improvements in size exclusion chromatography (SEC) column technology and modern applications of SEC separations. The better understanding of SEC column design and separation parameters is described in the theoretical sections of this chapter that will help the reader fine-tune the work. The same is true for column performance tests, which should be applied regularly, especially after a column purchase. To obtain reproducible results, it is recommended to choose column manufacturers who can assure constant quality and performance. More and more interesting and specialized SEC columns will appear on the market in the near feature, enabling work to be done more reliably and efficiently. All SEC columns have to be designed and synthesized by the polymer chemist to meet the specific requirements of the separation mechanism. For efficient SEC separations, a number of important aspects are considered: inertness of packing, good accessibility of pore structure, high pore volume and porosity, and diffusion control (fast mass transfer).