The use of mass spectrometry in protein identification has revolutionized the field of proteomics.Coupled to various affinity purification techniques, mass spectrometry is used to identify protein–proteininteractions. This chapter looks at the use of these affinity purification techniques in the identificationof protein interactions. Various tags are used to purify protein complexes including tandem affinity purification.The FLAG tag is another commonly used tag which is a small tag that tends not to interfere with theprotein function. These different affinity purification methods are used to purify proteins that are furtheridentified by either ESI-MS or MALDI-MS.