This text presents a series of reflections on the therapeutic potential of the ritual use of ayahuasca in the treatment and handling of substance dependence problems. Anthropological and psychiatric data on the ritual use of ayahuasca for ‘healing’ dependence in psychotherapeutic centers (in Peru and Brazil), as well as in ayahuasca religions (in Brazil), are reviewed and critiqued. Methodological, ethical and political considerations for current and future research in this area are then discussed, and an interdisciplinary agenda for studies on the use of ayahuasca to treat or handle substance dependence is proposed.