This paper examines the traditional use of medicinal plants in Northern Peru and Southern Ecuador, with special focus on the Departments of Piura, Lambayeque, La Libertad, Cajamarca, and San Martin, and in Loja province, with special focus on the development since the early colonial period. Northern Peru represents the locus of the old Central Andean "Health Axis." The roots of traditional healing practices in this region go as far back as the Cupisnique culture early in the first millennium BC. Northern Peru and Southern Ecuador share the same cultural context and flora but show striking differences in plant use and traditional knowledge. Two hundred fifteen plant species used for medicinal purposes in Ecuador and 510 plant species used for medicinal purposes in Peru were collected, identified,. and their vernacular names, traditional uses, and applications recorded. This number of species indicates that the healers, market vendors, and members of the public interviewed in Peru still have a very high knowledge of plants in their surroundings, which can be seen as a reflection of the knowledge of the population in general. In Ecuador much of the original plant knowledge has already been lost. In Peru, 433 (85%) were Dicotyledons, 46 (9%) Monocotyledons, 21 (4%) Pteridophytes, and 5 (1%) Gymnosperms. Three species of Giartina (Algae) and one species of the Lichen genus Siphula were used. The families best represented were Asteraceae with 69 species, Fabaceae (35), Lamiaceae (25), and Solanaceae (21). Euphorbiaceae had 12 species, and Poaceae and Apiaceae each accounted for 11 species. In Ecuador the families best represented were Asteraceae (32 species), Euphorbiaceae, Lamiaceae, and Solanaceae (11 species each), and Apiaceae, Fabaceae, Lycopodiaceae (9 species each). One hundred eighty-two (85%) of the species used were Dicotyledons, 20 Monocotyledons (9.3%), 12 ferns (5.5%), and one unidentified lichen was used. Most of the plants used (83%) were native to Peru and Ecuador. Fresh plants, often collected wild, were used in two thirds of all cases in Peru, but in almost 95% of the cases in Ecuador. The most common applications included the ingestion of herb decoctions or the application of plant material as poultices. Although about 50% of the plants in use in the colonial period have disappeared from the popular pharmacopoeia, the overall number of plant species used medicinally has increased in Northern Peru, while Southern Ecuador shows a decline of plant knowledge since colonial times.