The junctional epithelium is located at a strategically important interface between the gingival sulcus, populated with bacteria, and the periodontal soft and mineralized connective tissues that need protection from becoming exposed to bacteria and their products. Its unique structural and functional adaptation enables the junctional epithelium to control the constant microbiological challenge. The antimicrobial defense mechanisms of the junctional epithelium, however, do not preclude the development of gingival and periodontal lesions. The conversion of the junctional to pocket epithelium, which is regarded as a hallmark in disease initiation, has been the focus of intense research in recent years. Research has shown that the junctional epithelial cells may play a much more active role in the innate defense mechanisms than previously assumed. They synthesize a variety of molecules directly involved in the combat against bacteria and their products. In addition, they express molecules that mediate the migration of polymorphonuclear leukocytes toward the bottom of the gingival sulcus. Periodontopathogens-such as Actinobacillus actinomycetemcomitans or, in particular, Porphyromonas gingivalis-have developed sophisticated methods to perturb the structural and functional integrity of the junctional epithelium. Research has focused on the direct effects of gingipains, cysteine proteinases produced by Porphyromonas gingivalis, on junctional epithelial cells. These virulence factors may specifically degrade components of the cell-to-cell contacts. This review will focus on the unique structural organization of the junctional epithelium, on the nature and functions of the various molecules expressed by its cells, and on how gingipains may attenuate the junctional epithelium's structural and functional integrity.