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.