Despite much success in the control of mastitis in dairy cattle, intramammary infection with Streptococcus uberis remains a threat to herd health. This organism is a frequent cause of mastitis worldwide. Recent advances in the ability to genetically manipulate this bacterium, coupled to the determination of a representative genome sequence have already enabled the investigation of certain aspects of disease pathogenesis. Further use of such technology coupled to reliable models of disease and post-genomic analysis will permit the elucidation of further interactions between pathogen and host. This additional information can be usefully targeted at identification of candidates for inclusion in effective vaccines. This communication reviews the current, reported progress using this technology for S. uberis.