The high prevalence and the socio-functional impairment associated with depressive disorders, added to the limitations of currently available treatments, justify the search for novel pharmacological strategies for the management of depression. This chapter presents the major results of animal and human studies conducted by a group of Brazilian researchers concerning the antidepressant potential of harmine, an alkaloid belonging to the group of β-carbolines and present in Ayahuasca (AYA), a tea with hallucinogenic properties used for religious and medicinal purposes by peoples from the Amazon. The results obtained thus far suggest that harmine and other substances present in AYA might have antidepressant-like effects in the central nervous system of animals and human patients, pointing out the possibility of the therapeutic use of AYA in humans.