Antimicrobial resistance (AMR) represents a major challenge to global health. This problem is most apparent in healthcare facilities, with a comparatively small number of pathogens being responsible for a substantial burden of hospital acquired infections globally. One of the key pathogens is the Gram-negative coccobacilli, Acinetobacter baumannii. It has been estimated that between 47% and 93% of A. baumannii infections are associated with multi-drug resistance (MDR), which is facilitated through a variety of well documented mechanisms (β-lactamases, efflux pumps, aminoglycoside-modifying enzymes, permeability defects, and target modifications). As our current pool of antimicrobial treatments becomes increasingly less effective, it is vital to identify new targets that can aid in the development novel treatments and strategies. In this we review we outline the key virulence mechanisms in A. baumannii (gene acquisition and adaptation, resistance to stresses, biofilm formation, and host interaction) and discuss their potential as targets for new therapeutics to reduce the impact of infections caused by MDR A. baumannii.