Introduction: Carbapenems have an important place in our antibiotic armamentarium and have been trusted to effectively treat infections caused by ESBL-producing Enterobacteriaceae for many years. However, the utility of carbapenems has been compromised by the emergence of resistance especially in Enterobacteriaceae. Therefore, carbapenem-sparing alternative antibiotics are of extreme importance in clinical practice. Areas covered: We reviewed studies addressing currently available antibiotic options used as both empiric and definitive therapy for the treatment of infections due to ESBL-producing Enterobacteriaceae published in the PubMed/MEDLINE, Web of Science and Scopus databases without any date restriction. Current treatment alternatives included beta-lactam/beta-lactamase inhibitor combinations, cefepime, cephamycins, fluoroquinolones, aminoglycosides, fosfomycin, pivmecillinam, temocillin and, various oral alternative agents. We also summarized the clinical and molecular epidemiology, early prediction methods and impact of initial empirical therapy and de-escalation approach for ESBL-producing Enterobacteriaceae infections. Expert opinion: The current literature would endorse the carbapenem utilization for patients with severe and high inoculum-high risk infections. However, for milder infections particularly for urinary tract infections, various carbapenem-sparing antibiotics can be considered in selected cases. For infections including easily drainable intra-abdominal infections and catheter-related infections in which catheter removal is readily available more reliable data are needed to recommend non-carbapenem antibiotics confidently.