Despite not being a disease in and of itself, antibiotic resistance could be considered the global epidemic of modern times, since it produces the failure to prevent and treat many infectious diseases. This can ultimately lead to untreatable microbial infections becoming more widespread and this will significantly increase morbidity and mortality. This worldwide problem is estimated to cause millions of deaths per year and could become an even more significant menace to humanity than established illnesses, such as cancer. In February 2017, the World Health Organization (WHO) published a list of antibiotic-resistant “priority pathogens” – a catalogue of 12 families of bacteria which pose the greatest threat to human health - and Acinetobacter baumannii is leading the list. The most critical group includes multidrug-resistant bacteria, which pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. This group includes Acinetobacter, Pseudomonas, and various Enterobacteriaceae and they are often associated with deadly infections, such as bloodstream infections and pneumonia. Furthermore, these bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best available antibiotics for treating multidrug-resistant bacteria. A. baumannii is a particularly worrisome example and demands attention: This pathogen turned into a menace to humans during the late 70s, likely as a result of intense antibiotic use in hospital settings, and became one of the microorganisms that are challenging the antibiotic era. Its extreme genome plasticity, combined with mechanisms of horizontal genetic transfer, have played a key role in the evolution of this microorganism, as well as its adaptability to unfavorable environments. However, its pathophysiology, as well as the mechanisms leading to its success as a pathogen, are not that simple to unveil. However, what is clear is that the triad of host-pathogen-environment is crucial in selection and establishment of multidrug-resistant clones and outbreaks. Indeed, there are still many aspects of this pathogen that require a deeper understanding - not only regarding mechanisms of resistance but also its global pathophysiology. For example, basic understanding of transmission mechanisms; knowledge of ‘external’ factors modulating persistence of the pathogen; genetic effects on host susceptibility and infectiousness; mechanisms of pathogenicity and their dynamics; and genetic variation of the pathogen affecting virulence and transmissibility are some aspects that would require further study. Furthermore, the importance of other members of the genus as important nosocomial pathogens, such as Acinetobacter nosocomialis, has been increasingly recognized during the last few years.