Large molecules, like proteins and DNA, are separated from smaller constituents using size exclusion chromatography (SEC), also known as gel-filtration chromatography, a relatively low resolution column chromatography method. Generally, this “polishing” step is the final step of protein purification, cleaning up the isolated protein by removing salts or other compounds that have co-migrated during the purification processes. The columns are packed with resins, largely within the dextran family, that form pores of different sizes. Choosing the type of resin is one of the most important decisions when setting up a SEC system. Pre-packed and disposable columns are available for the removal of salts, dyes, phenol, unincorporated radiolabels, as well as exchanging buffer solutions from protein and nucleic acid samples. Spin and gravity columns can be used as an alternative to dialysis for small scale fractionations, as they decrease sample dilution.