Ayahuasca is a psychedelic plant brew originating from the Amazon Rainforest. It is formed from two basic components, the Banisteriopsis caapi vine, and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of this brew and describe recent work on its pharmacology and phenomenological responses to, and clinical applications of ayahuasca. There has been a significant increase in interest surrounding ayahuasca since the turn of the millennium. Increasing numbers of tourists are travelling to the Amazon rainforest to drink the brew, with various media outlets, celebrities, and researchers describing benefits from its consumption. Ayahuasca is now present across the globe and retreat centres offering plant medicine experiences has become a thriving business. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality, mental health outcomes, and nature-relatedness are discussed in this review. Further, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and its therapeutic uses.