Over 700,000 deaths worldwide are attributed to resistant bacterial infections per year and this number is increasing. Resistance is spurred by overuse and misuse of antibiotics and the situation is then made worse by the lack of scientific innovation due to poor economic incentives. Founded in 2016, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global non-profit partnership dedicated to accelerating antibacterial research to tackle this global rising threat. Since inception it has provided non-dilutive funding and support to groups that are developing products to prevent, diagnose, and treat infections caused by drug-resistant bacterial pathogens. CARB-X has placed a high value on innovation, and this includes embracing non-traditional modalities for which there is neither a well-trodden preclinical nor a well-defined clinical history. The CARB-X portfolio supports a wide variety of novel programs to help the global antibacterial research ecosystem understand the potential that these modalities can play in the management or prevention of serious infections. As the CARB-X portfolio expanded, strategies to create a higher-level understanding of common issues facing product developers and to leverage efficiencies broadly across funded groups has evolved. This presentation will highlight some key lessons from the initial 5 years of CARB-X as well as some future opportunities that should positively impact the broader ecosystem of antibacterial drug development.