Significant and rapid progress has been made in our knowledge and understanding of Mycobacterium bovis since the last international M. bovis conference 5 years ago. Much of this progress has been underpinned by the completion of the genome sequence. This important milestone has catalysed research into the development of a number of improved tools with which to combat bovine tuberculosis. In this article we will review recent progress made in the development of these tools and in our understanding of the organism, its evolution and spread. Comparison of the genome sequence with those of other members of the Mycobacterium tuberculosis complex has enabled insights into the evolution of M. bovis. This analysis also indicates that the M. tuberculosis complex have the propensity to adapt to new host species. The use of high throughput molecular typing methods has revealed that the recent bovine tuberculosis epidemic in Great Britain is being driven by a number of clonal expansions, which cannot be explained by random mutation and drift alone. Completion of a number of mycobacterial genome sequences has allowed the development of antigen mining techniques that rapidly identify M. bovis-specific genes. These can then be used as reagents in the gamma interferon assay to increase the specificity of the assay and also to discriminate between Bacillus of Calmette and Guérin (BCG) vaccinated animals and those infected with M. bovis. In the longer term, comparisons between the genomes of M. bovis and BCG will allow insight into how BCG became attenuated following serial passage on artificial growth media and reveal clues into how to improve the vaccine efficacy of BCG.