The foremost reason for this paper is to identify and understand four specific cultural systems which identify ayahuasca as a focal component of a certain framework. In order to do so holistically it is imperative to elucidate the ethnomedical and biomedical understandings of how ayahuasca interacts with the person who consumes it. Using an ethnobotanical approach to examine the relationships between the plants themselves and the people will shed light on the various modes of understanding present amongst the four cultural systems: traditional cultures, mestizo shamanism, Santo Daime, and União do Vegetal. The basic plant components used to make ayahuasca will be examined in order to illustrate: what they are, where they are found, and why they are valued in traditional Amazonian medicine, blended medical systems and religious syncretism. Through analysis of the dieta that typically accompanies ayahuasca consumption in indigenous Amazonian cultures as well as more recently established forms of ayahuasca cultural systems it becomes even clearer how this seemingly ancient medicine is intimately connected to the various frameworks it is part of.