The public health impact of addiction, with its high relapse rates and the limited efficacy of available treatments, has prompted the search for alternative therapeutic approaches. In recent times, there has been renewed interest in the anti-addictive potential of psychedelics. Consumption of ayahuasca, the N,Ndimethyltryptamine- containing Amazonian plant tea, is experiencing unprecedented expansion. The ritual use of this brew, obtained from Banisteriopsis caapi and Psychotria viridis, in shamanistic and religious contexts is now popular in Europe and North America. Studies of long-term ayahuasca-church members in Brazil have recorded discontinuation of drug use after starting ayahuasca use. Furthermore, several centers that offer therapies based on ayahuasca as a means to treat addictive behavior claim higher success rates than more traditional approaches. In this chapter, we review the pharmacology of ayahuasca and the data available concerning its efficacy in the treatment of drug addiction. Although the therapeutic potential of ayahuasca, based on the evidence examined, is promising, the lack of systematic studies precludes firm conclusions. Ideally, research methodology should be improved, with future studies implementing well-planned clinical protocols with adequate controls, end-points, and follow-up.