The goal of this review is to analyse how recent technical developments contributed to the biochemical charac- terisation of protein complexes. Improvement of tags used for protein puri¢cation, including in our own laboratory, and the development of new strategies have allowed the use of generic procedures for the puri¢cation of a wide variety of protein com- plexes. Together with increased mass spectrometry sensitivity and automation, this made high throughput studies of protein complexes possible and allowed proteome-wide analyses of pro- tein complexes. However, knowledge of protein complex com- position, even at the cellular level, will not be su⁄cient to under- stand their function. We suggest that the next level of analysis in this area will be the de¢nition of internal subunit arrangement in complexes as a ¢rst step toward more detailed structural analyses. " 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.