Based on observations of the positive therapeutic effects that ayahuasca ceremonies can have on people with addiction issues, informal and formal support for recovery from addictions is currently provided in diverse settings.These include rituals offered by indigenous healers, ayahuasca circles, or psychotherapists, and more or less structured ayahuasca-assisted, inpatient and outpatient addiction treatment programs. Such approaches are rooted either in indigenous Amazonian medicine traditions, the Brazilian Ayahuasca Religions, psychedelic-assisted psychotherapy, or consist in a hybrid combination of these. Although ayahuasca-assisted treatment can be very valuable therapeutically, it is, however, important to point out that it is useful only for certain individuals and under certain circumstances. Ayahuasca, in and of itself, is an instrument, a tool.The potential outcome can be beneficial or harmful depending on different variables. The subjective experience and hence the therapeutic value of ayahuasca, as with other psychedelic substances, is intrinsically related to the triad of drug, set, and setting. The study was intended to generate empirically based hypotheses on the therapeutic mechanisms of ayahuasca in substance dependency treatment. As outlined in this paper, ayahuascaassisted treatment can trigger various types of psycho-spiritual processes that are valued in other therapeutic approaches for substance dependency. Further clinical investigation is still warranted to assess the efficacy of ayahuasca for substance dependency treatment in comparison to current best treatment practices. It seems, however, based on preliminary research that ayahuasca interventions for substance abuse treatment are, in some cases, very effective and that they can be integrated into multidisciplinary multicultural addiction treatment programs.