Members of the claudin family of proteins are the main components of tight junctions (TJs), the major selective barrier of the paracellular pathway between epithelial cells. As such, the claudins have the ability to generate the TJ physiological barrier and to control various physiological processes. Therefore, the importance of this family of proteins is obvious and many efforts were made to reveal different aspects of claudin TJ protein biology. In this review, we discuss recent advances in our understanding of claudin structure and function, as well as their distribution pattern in different organs and tissues. We mainly highlight the complex interactions of claudins in various physiological systems and suggest a possible role for a coregulation mechanism.