Chemical crosslinking provides information about protein-protein interactions in the context of intact protein complexes; therefore, it is particularly suited to the analysis of multiprotein complexes. Rather than a single distinct technique, chemical crosslinking represents a smorgasbord of techniques that differ significantly both in chemistry and in scope. This unit will attempt to guide the reader through the complexities of crosslinking to find the most suitable approach for a given biological question. Sample protocols for two crosslinking methods considered to be particularly useful for the analysis of large multiprotein complexes are provided: His6-mediated crosslinking and photoinducible label transfer crosslinking.