The last two decades have seen a steady increase in the number of publications devoted to ayahuasca. This fascinating psychotropic plant tea has attracted the attention of biomedical and psychological scientists. Researchers have gathered data on the physiological impact of ayahuasca administration to humans and have assessed the consequences of long term regular use. Acute administration studies have provided information on the fate of the alkaloids in the organism, the modification of vital signs, neuroendocrine and immunological parameters and neurophysiological variables. For the first time, neuroimaging techniques have shown us which brain areas “light up” during the most intense phases of the ayahuasca experience. Also, the popularization of ayahuasca has raised concerns that its regular use may cause neuropsychiatric and addiction-related problems for users. An increasing number of studies have tried to address these concerns. In the present chapter we aim to give an overview of the available literature on the human pharmacology of acute ayahuasca intake and on the neuropsychiatric and psychosocial consequences of its long-term use.