Mastitis remains a major challenge to the worldwide dairy industry despite the widespread implementation of mastitis control strategies. The last forty years have seen a dramatic decrease in clinical mastitis incidence but this has been accompanied by a change in the relative and absolute importance of different pathogens. Escherichia coli and Streptococcus uberis are now the two most common causes of bovine mastitis and are an increasing problem in low somatic cell count herds. This paper reviews the changes in incidence and pattern of mastitis in the UK over the last four decades and discusses some of the possible explanations for these changes. It focuses in particular on apparent changes in the behaviour of E. coli and its ability to cause persistent intramammary infection; which may be as a result of bacterial adaptation or the unmasking of previously unrecognized patterns of pathogenesis. The prospects for novel approaches to mastitis control are discussed, as are the current and future challenges facing the industry.