In addition to the use of conventional drug resistance determination, the survey has included whole genome sequencing (WGS) of all M. tuberculosis isolates from two provinces: Gauteng and KwaZulu-Natal. This WGS project was initiated as part of a multi-country, WHO co-ordinated effort to determine baseline resistance to fluoroquinolones and pyrazinamide, as these drugs are planned for inclusion in new regimens currently under investigation. This study has been concluded and figures for pyrazinamide and fluoroquinolone resistance are approximately 3% and 1% respectively, irrespective of prior treatment history. These are positive findings for South Africa, which has recorded one of the lowest prevalence figures of resistance compared to other countries for which surveillance information is available. Furthermore, it suggests that first-line regimens, including these drugs in combination with new agents are likely to show success and South Africa would be likely to be one of the countries to adopt such an approach expeditiously. The CTB has successfully established and optimised WGS as a method for use in surveillance and is recognised internationally for its contribution in this field. Based on research conducted by CTB in which closely comparable findings between the two approaches have been demonstrated, WGS has been shown to be a suitable alternative to phenotypic DST in surveys. It is likely to change the landscape of laboratory-based TB management in the future. Additional development of the technology is under way to improve the CTB’s ability to maximise the use of WGS in investigating TB transmission as well.