Introduction: The constantly increasing spread of severe infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) is a critical threat to the global medical community. After a long period of antibiotic pipeline pause, new antibiotic compounds are commercially available or are at late stages of clinical evaluation, promising to augment the therapeutic armamentarium of clinicians against deadly pathogens. Areas covered: This review summarizes available data regarding agents with potent activity against critical MDR Gram-negative pathogens, which urgently require new efficient antibiotics. Recently approved antibiotic formulations; and agents in advanced stages of development, including combinations of β-lactam/β-lactamase inhibitor, novel cephalosporins (cefiderocol), tetracyclines (eravacycline), aminoglycosides (plazomicin), quinolones (delafloxacin and finafloxacin) and pleuromutilins (lefamulin) are discussed in this review. Expert opinion: The recent introduction of new antibiotics into clinical practice is an encouraging step after a long period of pipeline stagnation. New formulations will be a useful option for clinicians to treat serious infections caused by several MDR Gram-negative pathogens. However, most of the new compounds are based on modifications of traditional antibiotic structures challenging their longevity as therapeutic options. More investment is needed for the discovery and clinical development of truly innovative and effective antibiotics without cross-resistance to currently used antibiotics.