Controversy surrounds combination treatment or monotherapy against multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Acinetobacter infections in clinical practice. We searched the PubMed and Scopus databases for studies reporting on the clinical outcomes of patients infected with MDR, XDR, and PDR Acinetobacter spp. with regard to the administered intravenous antibiotic treatment. Twelve studies reporting on 1,040 patients suffering from 1,044 infectious episodes of MDR Acinetobacter spp. were included. The overall mortality between studies varied from 28.6 to 70 %; from 25 to 100 % in the monotherapy arm and from 27 to 57.1 % in the combination arm. Combination treatment was superior to monotherapy in three studies, where carbapenem with ampicillin/sulbactam (mortality 30.8 %, p = 0.012), carbapenem with colistin (mortality 23 %, p = 0.009), and combinations of colistin with rifampicin, sulbactam with aminoglycosides, tigecycline with colistin and rifampicin, and tigecycline with rifampicin and amikacin (mortality 27 %, p < 0.05) were used against MDR Acinetobacter spp. resistant at least to carbapenems. The benefit was not validated in the remaining studies. Clinical success varied from 42.4 to 76.9 % and microbiological eradication varied from 32.7 to 67.3 %. Adverse events referred mainly to polymixins nephrotoxicity that varied from 19 to 50 %. The emergence of resistance was noted with tigecycline regimens in off-label uses in three studies. The available data preclude a firm recommendation with regard to combination treatment or monotherapy. For the time being, combination treatment may be preferred for severely ill patients. We urge for randomized controlled trials examining the optimal treatment of infections due to MDR, XDR, and PDR Acinetobacter spp.