Claudins are cell–cell adhesion molecules located at the tight junctions (TJs) between cells in epithelial cell sheets. The claudin family in mammals consists of 27 four-transmembrane domain proteins. Claudins are responsible for the paracellular barrier function of TJs, and in some cases confer paracellular channel functions to the paracellular barriers of TJs. Based on recent breakthroughs in the molecular structure of claudins, the hypothetical ‘antiparallel double row model’ was proposed, which suggests how claudins polymerize in a linear fashion and form TJ strands with paracellular barrier and channel functions. Meanwhile, ongoing studies at the cell and tissue levels are clarifying how the paracellular barrier and/or channel functions of claudin-based TJs, which are both robust and flexible, organize various biological systems. The claudin protein family, which has 27 members in mammals, consists of tight junction (TJ) proteins that are indispensable for the paracellular barrier in vertebrate epithelial cell sheets. The detailed structures of claudin-15, -19, and -4 were recently solved at the amino acid level, opening the door to research into how claudins form TJ strands and elicit the paracellular barrier and channel functions of TJs. All claudin family members are expected to share the same basic structural framework, including cis- and trans-interactions with each other, but have different extracellular regions that account for their various roles in forming paracellular barriers and channels. Claudin knockout (KO) mouse studies and human variations in claudin expressions provide clues about how various biological systems are robustly and flexibly constructed with respect to claudin-based TJs.