The family of more than 20 claudin (CLDN) proteins comprises one of the major structural elements within the apical tight junction apparatus, a dynamic cellular nexus for maintenance of a luminal barrier, paracellular transport, and signal transduction. Loss of normal tight junction functions constitutes a hallmark of human carcinomas. CLDN1 may support tumor suppressive functions in tissues such as the brain, where dramatic loss of expression has been demonstrated in glioblastoma multiforme. The role(s) for CLDNs 3 and 4 in tumorigenesis is less clear. CLDN4 appears to be over-expressed in ovarian and pancreatic carcinomas, and this raises the possibility that a unique, potentially non-toxic cancer cell target may be developed through the design of enterotoxin analogues. Future goals include understanding the biochemical and physiological mechanisms that are perturbed as a consequence of CLDN alterations in the progression of solid tumors.