Carbapenem-resistant Acinetobacter baumannii (CRAb) is a challenging, environmentally hardy organism with a propensity to spread within hospitals and a predilection to infect critically ill, vulnerable patients. With its potential for rapid transmission, limited treatment options, and substantial mortality, CRAb is recognized as a critical, top-priority pathogen. Since its initial discovery in 1985, CRAb has disseminated globally, presenting a significant public health threat. CRAb is now endemic in many regions in Europe, South America, Asia, and Africa and globally contributes to over 50 000 deaths each year. Its ability to adhere to hospital surfaces, withstand desiccation, and form biofilms leads to widespread outbreaks. At-risk populations include those hospitalized and ventilated, and the most frequent presentations are respiratory and bloodstream infections. Carbapenem resistance in CRAb is primarily mediated by plasmid-borne carbapenemase genes, especially blaOXA-23. These genes, carried by several epidemic international clones, including IC1 and IC2, have facilitated the global dissemination of CRAb through horizontal gene transfer in healthcare settings. Mortality rates are >20% and vary substantially by region and by type of infection, with bloodstream infections carrying >40% mortality. Despite its significant impact, the development of treatments for CRAb remains inadequate. The novel agent sulbactam-durlobactam holds promise for improved patient outcomes, but ongoing therapeutic development, infection prevention, and antimicrobial stewardship are critical to combat this formidable pathogen. Here, we review the emergence and dissemination of CRAb, its molecular epidemiology and resistance mechanisms, summarize contemporary global clinical epidemiology and patient outcomes, and briefly describe existing and future therapeutics.