Our perception that host–bacterial interactions lead to disease comes from rare, unsuccessful interactions resulting in the development of detectable symptoms. In contrast, the majority of host–bacterial interactions go unnoticed as the host and bacteria perceive each other to be no threat. In July 2004, a focused international symposium on epithelial–bacterial pathogen interactions was held in Newcastle upon Tyne (UK). The symposium concentrated on recent advances in our understanding of bacterial interactions at respiratory and gastrointestinal mucosal epithelial layers. For the host these epithelial tissues represent a first line of defence against invading bacterial pathogens. Through the discovery that the innate immune system plays a pivotal role during host–bacterial interactions, it has become clear that epithelia are being utilized by the host to monitor or communicate with both pathogenic and commensal bacteria. Interest in understanding the bacterial perspective of these interactions has lead researchers to realize that the bacteria utilize the same factors associated with disease to establish successful long-term interactions. Here we discuss several common themes and concepts that emerged from recent studies that have allowed physiologists and microbiologists to interact at a common interface similar to their counterparts – epithelia and bacterial pathogens. These studies highlight the need for further multidisciplinary studies into how the host differentiates between pathogenic and commensal bacteria.