There is a constant need for resupply with resistance-breaking antibiotics. Governmental programs and updated regulatory guidance have incentivized mainly small- and medium-sized biopharmaceutical companies to develop novel antibiotics up to market licensure, while major pharma players, with exceptions, have abandoned the space for a perceived lack of a return on their investment. The portfolio of approved drugs has improved over recent years for gram-positive infections, including infections caused by methicillin-resistant Staphylococcus aureus. On the other hand, unmet medical need has surfaced in indications dominated by gram-negative pathogens including complicated intra-abdominal and bloodstream infections as well as hospital-acquired and ventilator-associated pneumonia. Few if any treatment options are left for extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae, e.g., Klebsiella pneumoniae, and the multi-drug-resistant non-fermenting gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter baumannii. The present paper summarizes and reviews the clinical pipeline of novel antibiotics by clinical indication and identifies the unmet medical need in the space.