<p><i>Acinetobacter baumannii</i> is notorious for its antimicrobial resistance and its potential to cause epidemics in hospital settings, which pose a global health threat. Although this microorganism is traditionally considered a low-virulence pathogen, extensive research has been conducted on its virulence and pathogenesis in recent years. Advances in understanding the virulence mechanisms of <i>A. baumannii</i> have prompted a shift in the development of anti-infective agents. The outer membrane protein A (AbOmpA) of <i>A. baumannii</i> is a key virulence factor both in vitro and in vivo. AbOmpA exists in three forms: outer membrane-integrated AbOmpA, outer membrane vesicle (OMV)-associated AbOmpA, and free proteins. Given that outer membrane-integrated AbOmpA has been implicated in the virulence and antimicrobial resistance of <i>A. baumannii</i>, many studies have focused on outer membrane-integrated AbOmpA as a therapeutic target for combating drug-resistant <i>A. baumannii</i>, and have led to the discovery of small molecules, polypeptides, and antimicrobial peptides targeting AbOmpA. However, the pathophysiological role of OMV-associated AbOmpA and its impact on AbOmpA-targeting agents remain unclear. This review summarizes the current knowledge of AbOmpA and critically discusses OMV-associated AbOmpA in relation to virulence and its potential impact on AbOmpA-targeted therapies to provide a better understanding of AbOmpA for the development of novel therapeutics against <i>A. baumannii</i>.</p>