Stellenbosch University, Department of Biomedical Sciences has an extensive Mycobacterium tuberculosis strain bank containing approximately 20 000 isolates, collected from 2001 to present. Clinical isolates comprising this bank have been characterised by spoligotyping, line probe assay and DSTs. This has allowed us to study the molecular epidemiology of M. tuberculosis, and has led to a paradigm shift in our understanding of exogenous re-infection, dual infections, drug tolerance, host genetics, mechanisms and spread of drug resistance. Current research in this group also focusses on providing a better understanding of the biology of M. tuberculosis and how it evolves and adapts to acquire resistance to first and second line drugs. For this, our group is using an “omics” approach. This provides insights about changes in the genome by whole genome sequencing, how the transcriptome and proteome change during the evolution of resistance or respond to exposure of the bacterium to various anti-Tuberculosis drugs. Bioinformatics is central to all these activities and there is a strong drive to strengthen capacity in this field. Functional analysis is being performed to validate the results of the bioinformatic studies.