It is clear that crew health and safety need to be ensured during (long-term) space missions. To guarantee the health of the astronauts, several prevention, monitoring and mitigation measures are implemented by the space agencies to control microbial contamination and the development of improved spaceflight-suitable methods for microbiological monitoring, as well as contamination control and reduction is an important research area. One group of antimicrobials that are explored are metals, such as copper and silver, for which various studies indicated their potential. However, bacterial resistance mechanism to these and other antimicrobials have been described repeatedly. Moreover, these resistance mechanisms are often strictly regulated, and currently, the main focus has been on the transcriptional network. Yet, recent research has shown the importance of post-transcriptional regulation via small regulatory RNAs, a regulatory level which has been ignored so far when studying bacterial metal resistance. Nonetheless, it has been shown that the behavior of bacteria differs under space conditions with a central role for Hfq, a RNA chaperone that interacts with those small regulatory RNAs. Therefore, the bacterial response to such metal-based antimicrobials needs to be thoroughly evaluated before possible implementation. Such tests are ideally performed on microorganisms isolated from space habitats, e.g. Cupriavidus metallidurans strains recently isolated from the ISS drinking water systems.