Increasing reports of Acinetobacter infections that cause pneumonia, meningitis, endocarditis, and bacteriaemia underline the clinical importance of this pathogen. Members of the genus Acinetobacter, particularly Acinetobacter baumannii, are now recognized as significant nosocomial pathogens, particularly for the subset of critically-ill patients requiring mechanical ventilation in hospital intensive care units. A. baumannii has itself a quite high level of naturally-occurring antibiotic resistance. The organism can survive for long periods in the hospital environment including dry and humid areas. One of the most worrying antibiotic resistance problems in A. baumannii is the increasing trend of carbapenem resistance, present also in few Croatian hospitals. Infections caused by this Gram-negative bacillus are common in the intensive care units anticipated by colonized patients. The increasing trend of carbapenem resistance in A. baumannii could be mediated from metallo-beta-lactamases (VIM, IMP, and SIM), carbapenem-hydrolyzing oxacillinases (OXA), porin modifications for influx of carbapenems (33-kDa CarO protein) and/or often combined mechanisms of resistance. The investigation of the background of carbapenem resistance in relevant clinical isolates of A. baumannii from Split University Hospital confirmed present of carbapenem-hydrolyzing oxacillinases OXA-107 representing a more recent evolutionary adaptation OXA-51-like enzyme to antibiotic challenge with carbapenems.