Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. The dissemination of carbapenem resistance plasmids amongst human pathogens and the emergence CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. It remains a challenge to obtain complete plasmid sequences and resolve the genetic context of mobile resistance genes from draft genome data. Single Molecule Real-time (SMRT) sequencing platform provides an alternative approach for reconstructing complete genomes, but it is not without its own challenges. Here we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. Using SMRT sequencing the precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Remarkably, our analysis showed that the ISEcp1-blaOXA-181 mobile element conferring resistance to carbapenem antibiotics is itself responsible for driving resistance to the last-resort antibiotic, colistin by insertional inactivation of the mgrB regulatory gene. These findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics. Strategies for the effective use of SMRT sequencing data will be discussed, drawing on our experiences with a number of other CRE or multidrug resistantEscherichia coli ST131 clinical isolates.