Literature data on thiophene structure-activity relationships of the last 10 years are reviewed. With regard to the broad spectrum of molecular structures the investigated compounds have been arranged according to their various therapeutic properties as indicated by the specific biological test systems. The interchange with the thiophene ring included mainly the following aromatic ring systems: benzene naphthalene, furan, pyndine, thiazole, pyrrole, and the respective indole, benzofuran, and benzthiazole analogs. Summarizing these findings it can be concluded that no general activity pattern can be given. Neither the exchange of the 2-thienyl moiety by the 3-thienyl nor the replacement of the thiophene ring by various aromatic rings resulted in a consistent superiority of any of the molecular structures.