The broad range of cellular activities carried out by Fe-S proteins means that they have a central role in the life of most organisms. At the interface between biology and chemistry, studies of bacterial Fe-S protein biogenesis have taken advantage of the specific approaches of each field and have begun to reveal the molecular mechanisms involved. The multiprotein systems that are required to build Fe-S proteins have been identified, but the in vivo roles of some of the components remain to be clarified. The way in which cellular Fe-S cluster trafficking pathways are organized remains a key issue for future studies.