This article offers an intercultural interpretation of the sense of the sacred in the practice of yage shamanism in Colombia. This practice is based on the ritual use of a plant medicine which for centuries has been the basis of the medical, spiritual and cultural systems of indigenous peoples of the Amazon piedmont in Colombia, Ecuador and Perú. Since the 1990s, this practice has expanded to urban areas of Colombia and other countries. After a short introduction, I develop my interpretation of yage shamanism in three stages: first, I explore some narratives of the origin of yage, showing how it is lived and understood as a source of knowledge and the foundational element of indigenous cultures. Second, I attempt a phenomenological analysis of yage shamanic experience, presenting it as a form of spiritual experience. Finally, I briefly address the issue of whether or not this form of experience is valid.