Acinetobacter baumannii is a Gram-negative coccobacillus commonly found in soil and water. It has been a major cause of nosocomial infections for the past few decades and is becoming more and more difficult to treat due to its ability to rapidly acquire resistance determinants to different types of antibiotics. Main resistance mechanisms performed by Gram-negative bacteria include enzymatic inhibition, modifications of target molecules, overexpression of efflux systems and porin mutations. A. baumannii has intrinsic and acquired enzymes β-lactamases, that inhibit β-lactam action by hydrolysis, and aminoglycoside-modifying enzymes, that modify the aminoglycoside molecule by transfer of functional groups, represent enzymatic inhibition resistance strategy. Enzymes like 16S rRNA methylase has emerged in A. baumannii as aminoglycoside target modifying enzyme. Furthermore, mutations in specific genes result in modification of cell surface local charge, which repels certain antibiotics from interacting with the outer membrane. Intrinsically present efflux systems are contributing to resistance to wide range of antibiotics, when overexpressed due to the presence of IS elements or the mutation in promoter or operator sequences. Porin knockout mutations contribute to antimicrobial resistance in a way that it leads to reduced membrane permeability. Genetic structures such as insertion sequences, transposons, integrons and resistance islands are widely distributed throughout the genome of A. baumannii. Due to these mobile genetic elements, A. baumannii has a remarkable ability to acquire and accumulate, as well as disseminate resistance determinants by horizontal gene transfer.