The recognition of Ayahuasca as a being, capable of agency and intention, taking action both as a healing and teaching spirit and as an ethical entity making a stand in the contemporary struggle for ecological survival and for indigenous culture valorisation is the central interrogation of this paper. What makes Ayahuasca an entity? Who is she an entity for? The importance of these questions is due to their centrality throughout multi-sited fieldwork conducted since 2004 among contemporary international shamanic networks linking various South American locations, namely the Peruvian Amazon, and European capitals such as Brussels, Paris, and Rome. Field research has revealed that the comprehension, or acceptance, of Ayahuasca as an entity is what differentiates the drug tourist and the long-term apprentice or practitioner. The more Ayahuasca becomes a “presence” the more the she moves from a space of “exceptional experience” to a space of regular, and yet extraordinary, “praxis.” But what does it mean, for a western secularized audience, to interact with her? What did it take for Ayahuasca to become a living entity to them? And what did it take them to become related to her? Attempting an answer to these questions will lead us to arguing what we’ve named “the hypothesis of an entangled Ayahuasca.” Comprehending Ayahuasca as entangled implies the acknowledgment of the numerous beings and diverse relations and interactions that call her into existence in a shared world and therefore are constitutive of her “being alive” and of her “wanting what she wants”.