The evolution of multicellular organisms has been, and continues to be, paralleled by the evolution of the surrounding microbial flora. This intimate coexistence between higher host organisms and microbes has generated a myriad of adaptation strategies at both sides to cope with, or even benefit from the given conditions. On the host side, the development of an effective immune defence system allowed the maintenance of an astonishingly stable homeostasis on many body sites, and even the establishment of sterile surfaces at vulnerable anatomical sites. On the other hand, microbial diversity has led to the establishment of a large number of microbial life styles that allow persistence and proliferation in the presence of host defense mechanisms. The following review describes bacterial strategies to circumvent or modify host defenses that operate at the epithelial lining. It illustrates the enormous diversity of mechanisms that are part of the complex interplay between microbial organisms and the host. It also reflects the dramatic progress made in the understanding of the mammalian immune defense system which many times has been initiated by the surprising results from the study of microbial pathogenesis.