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The state of Chiapas is one of the most biologically diverse and bioculturally rich areas of Mexico. The region known as the Highlands of Chiapas is a mountainous region that harbors vegetation types dominated by pine and oak species and human populations belonging to the Tsotsil, Tseltal, and Tojol-ab’al Indigenous groups. These people have named species, classifying them into groups reflecting their place in the universe according to their worldview and have generated knowledge about their biology, ecology, and the ways in which they may be used to satisfy both material and nonmaterial needs. People of the Highlands of Chiapas have produced knowledge that reflects the cultural significance of diverse species of plants. In general, there are scarce records about use, management, and perception of plants of the region from the Colonial period; however, anthropological and ethnobotanical researches were very active during the twentieth century to the present. It has been through ethnographies, dictionaries, vocabularies, and project reports that ethnobotanical information has been documented. The forest is a fundamental source of resources for the survival of Indigenous groups; rural people practice a multiple use of elements from forests, firmly based on empirical knowledge about them and the natural processes that mold them, and frequently using traditional management techniques. Furthermore, a great diversity of vascular and nonvascular, wild and domesticated, and native and exotic plants is employed to satisfy basic food, fuel, medicine, ornamental, and other needs. In this region, the use and knowledge about a great variety of botanical species used to treat diverse ailments is outstanding. A brief description of the role of plant species within the worldviews of some Mayan groups in this region is discussed. Inglés