Most membrane–proteins exist in complexes rather than isolated entities. To fully understand their biological function it is essential to study the intact membrane–protein assemblies. The overexpression and purification of many essential membrane–protein complexes is still a considerable and often unsurmountable challenge. In these cases, extraction from source is the only option for many large multi-subunit cellular machines. Here, we describe recent advances in overexpression of multi-subunit membrane–protein complexes, the strategies to stabilize these complexes and highlight major achievements in membrane–protein structural research that were facilitated by the prospect of achieving subnanometer to near-atomic resolution by electron cryo-microscopy.