Carbapenem resistant Enterobacteriaceae (CRE) cause infections with limited treatment options and serious mortality and morbidity. Currently, colistin, tigecycline and phosphomycin and their combination with each other or with carbapenems are used in the treatment of CRE infections. Among the available treatment options, carbapenem-containing regimens are the preferred treatments, and in general, combinations appear to be superior to monotherapies. However, no deal treatment regimens have yet been established for CRE. The search for new molecules continues. Beta-lactamase inhibitors including avibactam, varobactam and relebactam; cephalosporin molecules including ceftolosan and cefiderocol; tetracycline and aminoglycoside molecules, eravasidin and plasomycin are new antimicrobial options. Murepavadin, the first pathogen-specific peptidomimetic antimicrobial, would be ideal for de-escalation of empirical therapy following identification and susceptibility testing in antipseudomonal therapy. Although promising treatment approaches have been found, it is not possible to prevent spontaneous bacterial mutations, and thus, the biggest weapon we have in our struggle with the microbial world is rational policies for antibiotic use.