A related editorial discusses this study. The results of this trial do not necessarily close the door on combination therapy for the treatment of all carbapenem-resistant Gram-negative bacteria. The advent of new antibiotics might preclude the question of how to improve colistin-based therapy: ceftazidime–avibactam offers superior outcomes than colistin-based regimens, as shown in an observational study of patients infected with carbapenem-resistant Enterobacteriaceae. Similarly, ceftolozane–tazobactam can be used to treat carbapenem-resistant P aeruginosa in the absence of acquired carbapenemases. Cefiderocol, a novel siderophore cephalosporin, has promising in vitro activity against carbapenem-resistant A baumannii, as well as metallo-β-lactamase-producing organisms, but regulatory approval is still needed and its efficacy in the clinical arena is yet to be shown. In terms of future research, the identification of genotypes and phenotypes linked to resistance can lead to the development of rational antibiotic regimens defined by molecular targets, and inform the design of clinical trials. Thus, antimicrobial chemotherapy can advance towards the paradigm of precision medicine.