- Background: next generation sequencing (NGS) is increasingly being used in clinical microbiology. Like every new technology that is being adopted in microbiology, the integration of NGS into clinical and routine workflows needs to be carefully managed. Aim: to review the practical aspects of implementing bacterial whole genome sequencing (WGS) in routine diagnostic laboratories. Sources: review of the literature and expert opinion. Content: in this review, we discuss when and how to integrate whole genome sequencing (WGS) in the routine workflow of the clinical laboratory. In addition, as the microbiology laboratories have to adhere to various national and international regulations and criteria for their accreditation, we deliberate on quality control issues for using WGS in microbiology, including the importance of proficiency testing. Furthermore, the current and future place of this technology in the diagnostic hierarchy of microbiology is described as well as the necessity of maintaining backwards compatibility with already established methods. Finally, we speculate on the question whether WGS can entirely replace routine microbiology in the future and the tension between the fact that most sequencers are designed to process multiple samples in parallel whereas for optimal diagnosis a one-by-one processing of the samples is preferred. Special reference is made to the cost and turnaround time of WGS in diagnostic laboratories. Implications: further development is required to improve the workflow for WGS, particularly shorten the turnaround time, reduce costs and streamline downstream data analyses. Only when these processes will reach maturity, reliance on WGS for routine patient management and infection control management will become feasible, enabling the transformation of clinical microbiology into a genome-based and personalised diagnostic field.