Gram-negative infections (GNIs) represent a high-value segment of the antibiotic market and are often treated in the hospital setting. Infections due to Gram-negative pathogens (GNPs) are frequently severe and difficult to treat – particularly those due to multi-drug-resistant (MDR) GNPs, the prevalence of which continues to increase. Despite the availability of broad-spectrum antibiotics from multiple drug classes (e.g., carbapenems, quinolones, cephalosporins, beta-lactam/beta-lactamase inhibitors) to treat hospitalized patients with GNIs, the rising rates of antibiotic resistance and scarce new drug launches have resulted in highly-limited treatment options for an increasing number of GNI patients. However, several late-stage products targeting drug-resistant GNPs are expected to launch near-term, notably expanding the physicians’ armamentarium for these infections. These include two promising cephalosporin/beta-lactamase inhibitor combinations, Cubist’s ceftolozane/tazobactam (formerly CXA-201) and Actavis/AstraZeneca’s ceftazidime/avibactam (CAZ-AVI), as well as Tetraphase’s novel tetracycline derivative, eravacycline. Multi-pronged efforts are currently underway to promote and incentivize the development of novel antibiotics, including those targeting MDR GNPs. The Infectious Disease Society of America’s proposed Limited Population Antibacterial Drug (LPAD) approval mechanism is one such initiative that could expedite clinical development timelines and decrease associated costs for novel antibiotics targeting MDR pathogens.