Tight junctions (TJ) close the gap between endothelial and epithelial cells against undesirable passage of water and solutes. The major protein families of the TJs include junctional adhesion molecules (JAM), claudins, angulins, and TJ-associated MARVEL proteins such as tricellulin and occludin. The majority of these proteins are related to the cytoskeleton through adapters such as zonula occludens (ZO) proteins. TJ proteins not only act as barriers but some of them also create water channels or paracellular ion channels. They are engaged in a variety of processes aside from barrier and channel functions. They may act as pathogen receptors and mediate immunological responses. TJ proteins are involved in a variety of inflammatory disorders as well as bacterial infections. They act as targets in the diagnostics and treatment of cancer tumor and they can also facilitate epithelial-mesenchymal transition, enabling metastasis and tumorigenesis. This book provides significant information to help develop a good understanding of tight junctions and its functions. It will serve as a reference to a broad spectrum of readers.