Achromobacter xylosoxidans is a nonfermentative Gram-negative bacillus considered to be an opportunistic agent. It is an emerging pathogen in cystic fibrosis (CF), increasingly recovered from the respiratory tract of CF patients. It can cause inflammation and therefore might be involved in the decline of the lung function.This species is innately resistant to many antibiotics, including cephalosporins (except ceftazidime), aztreonam, and aminoglycosides. Moreover the isolates recovered from CF patient sputum are often resistant to major antimicrobial components usually prescribed to treat pulmonary infections. There was very little known about acquired resistance and nothing about innate resistance mechanisms when we started this work.Antibiotic resistance mediated by Resistance-Nodulation-cell Division (RND)-type efflux pumps is widespread among nonfermentative Gram-negative bacilli. We have characterized three putative RND operons in A. xylosoxidans genome. By using a gene inactivation technique we have demonstrated that these operons encode efflux systems (AxyABM, AxyXY-OprZ and AxyCDJ) able to export antibiotics. Two of them are strongly involved in A. xylosoxidans innate antibiotic resistance: AxyABM (resistance to aztreonam and various cephalosporins) and AxyXY-OprZ (aminoglycoside resistance).