Claudins (CLDNs) are a 27-member family of tetra-transmembrane proteins that have pivotal roles in maintaining cellular polarity and sealing the spaces between adjacent cells. Deregulation of their functions is often associated with pathological conditions, including carcinogenesis and inflammation. Some CLDNs are co-receptors for hepatitis C virus. Because CLDN-driven regulation of intercellular seals might be manipulated to enhance drug absorption, CLDNs are attractive targets for drug development. Monoclonal antibodies recognizing the extracellular domain of CLDNs are the first choice for therapeutics, but their development has been delayed. Here, we overview recent advances in the creation of anti-CLDN antibodies and discuss CLDNs as drug development targets.