Almost five centuries of interactions and relationships between humans and plants in Mesoamerica have been documented, principally from the etic perspective. This essay focuses on ethnohistorical sources mostly from New Spain (which includes much of contemporary Mexico) during the sixteenth, seventeenth, eighteenth, and early nineteenth century during Mexico’s Viceroyalty period. Indigenous documents usually referred to as codices are rare due to their destruction by Spanish authorities; none the less 15 preConquest documents exist and depict the people’s interactions with plants as well as other elements of the physical and spiritual worlds. Along with indigenous postConquest codices, the documents generated by ecclesiastical, government, and commercial authorities provide abundant textual and pictorial records of plants that influenced the life of native people as well as that of the Spanish and mestizo population. Botanical identification of the plants is limited in certain documents due to lack of adequate descriptions and/or illustrations. None the less, certain plants can be discerned from vernacular names associated with earlier illustrations as well as their etymological analysis. As sources for ethnobotanical data, the codices of the early Viceroyalty Period were complemented by later census data, commercial and tax records, and governmental inventories of useful resources (especially food and medicinal plants). Various missionaries and travellers authorized by the Spanish crown chronicled their experiences which included occasional observations about the natural history of plants. It was not until the eighteenth and the early nineteenth century that herbarium specimens and associated botanical studies permitted taxonomic identification of many plants of ethnobotanical importance. About 3000 plant names were recorded of which almost 700 have taxonomic determinations. They were important sources of medicines, food, material sources, and ornamentals.