Ayahuasca is a psychoactive traditional plant medicine preparation used by the indigenous tribes of the Upper Amazon in their shamanic traditions. Its use has become popular amongst Westerners seeking alternative means of healing, and the medicine has now spread across the globe via syncretic spiritual healing traditions such as the Santo Daime Church. Despite the increased use of the medicine, little research exists on its effectiveness for healing depression. The existing literature does not contain a detailed self-reported phenomenological account of ayahuasca healing a case of depression. The aim of this paper is to share a personal account of healing depression using ayahuasca in a Santo Daime ritual in Johannesburg, South Africa. This experience was unplanned and unexpected and resulted in a profoundly transformative healing process. Based on my experience, I describe ayahuasca’s ingestion as having created a powerful mind-body-spirit connection that resulted in what appeared and felt like a profound reconfiguration of the bio-electrical energy system in my body and a powerful anti-depressant action on my mind. These effects were catalyzed by a strong intention to heal and trust in and take responsibility for myself. Other South African Santo Daime members have reported healing of depression with ayahuasca, although in longer and different processes. It appears that the medicine engages the individual’s unique collective self (life-history, physical and mental disposition, beliefs and intents) resulting in different outcomes for different individuals. Thus, from my own and others’ experience, I describe ayahuasca as a spiritual medicine; one that promotes enhanced awareness and deeper connection to one’ s core self, to others and the greater universe, while facilitating the manifestation of one’s intentions and beliefs. This encounter with ayahuasca provided me a first-hand experience of learning and healing from the medicine, making real to me the indigenous Amazonian description of plants as being teachers and doctors.