Rue was one of the main medicinals in the European folk tradition, and it was also considered an important means of protection against supernatural evil in many parts of the world. All of the primary ethnobotanical sources from Spain were reviewed for information about the uses and importance of this plant. The data were analyzed for both content and geographical distribution. The most frequent applications relate to medicinal, veterinary, or protective virtues. The results show a high correspondence of the main medicinal uses to the pharmaceutically demonstrated properties of the plant: emenagogue and abortifacient; digestive; improve circulation; treat rheumatism; treat infections and inflammation; to relieve pain, and remove parasites among others. Most of the uses cited for Spain occur in several areas of the country, showing a high degree of homogeneity of the ethnobotanical knowledge of these species in Spain. The main recipes and applications are discussed.