Abstract Carbapenems are considered the drugs of choice for the treatment of serious infections caused by ceftriaxone-resistant Enterobacterales. However, because of the dramatic increase in carbapenem-resistant organisms worldwide, finding alternatives to carbapenems is a must. The potential options include β-lactam/β-lactamase inhibitor combinations, temocillin, cephamycins and some non-β-lactam drugs. The most controversial is piperacillin/tazobactam; the results of the MERINO trial are challenged because the isolates of patients with worse outcomes were frequently not susceptible to piperacillin/tazobactam when studied by reference methods, and also because the drug was not administered in extended infusion. Other potential options are briefly discussed. We conclude that carbapenems are not necessary for all patients with infections caused by ceftriaxone-resistant Enterobacterales.