The prevalence of bovine mastitis has been reduced over the past 25 years due to the implementation of a five-point control plan aimed at reducing exposure, duration and transmission of intramammary infections by bacteria. This has markedly reduced the incidence of bovine mastitis caused by bacteria which show a contagious route of transmission, but has had little effect on the incidence of mastitis due to bacteria which infect the gland from an environmental reservoir. Streptococcus uberis is one such bacterium which is responsible for a significant proportion of clinical mastitis worldwide. The inadequacies of the current methods of mastitis control have led to the search for additional measures, particularly vaccines to prevent intramammary infection by this bacterium. Such an approach requires detailed knowledge of the pathogenesis of intramammary infection. Our understanding of this area has grown in recent years but a lack of information still hampers disease control. Both live vaccines and, recently, crude sub-unit vaccines have shown promise against bovine mastitis due to S. uberis. Vaccines against mastitis must, however, be able to control infection without the participation of a marked inflammatory response. This review provides an overview of the recent advances which have been made in our understanding of host-pathogen interactions which promote infection and disease and highlights areas for strategic research aimed at controlling this bacterial infection.