Fertile crescent represents a unique arena for ethnobotanical studies. Advent of humans in this area took place in the early pleistocene and population explosion occurred 4000 years earlier here than in the West Mediterranean. Agriculture in this area of megadiversity dates back to Natufian culture, about 8000 B.C.. It includes 2 of the eight centers of origin of cultivated plants and many biregional and pluriregional species. Total gene pool of wild and cultivated plants has a great potential in its flora. Area shows a great variability in the flora and vegetation, inspite of the fact that large stretches of these lands are bare deserts. The reason for rich plant diversity is the location of this area between the Mediterranean, Irano-Turanian, Saharo-Sindian and Sudano-Decanian regions. One of the striking features is the replacement of various floras suddenly. The relationship between humans and plants has existed here since Paleolithic age. The cultures here have had a great impact on the development of medicine. This is supported by the grave of a Neanderthal man in the southern part of Hakkari-Turkey. Many plant remedies have been given on the clay tablets from the civilizations in the fertile crescent. Modern ethnobotany was born here with the work of Dioscorides from Anarzabos in South Anatolia-Turkey. Out of 600 plants documented by him in “Materia Medica”, majority have originated from this area and most of these plants are still in use. The traditional Unani medicine is still being practiced widely here, with important components of the ancient Mesopotamian usages. The herb dealers are still popular. The area abounds in mountains. A rich perennial herbaceous and semi-woody dwarf plants are distributed at high altitudes of these mountains, which are covered by snow until the mid-spring when herbaceous plants start emerging. Several species of Acantholimon, Ajuga, Allium, Alyssum, Astragalus, Berberis, Cerasus, Chamaecytisus, Cirsium, Colchicum, Campanula, Convolvulus, Cotoneaster, Crocus, Dianthus, Draba,Ebenus, Euphorbia, Fritillaria, Hypercium,Orchis, Ornithogalum, Marrubium,Morina,Ononis,Phlomis,Pilosella, Potentilla Rosa, Sedum,Tanacetum,Thymus and several other plant taxa occupy these altitudes in the alpine and subalpine vegetation. Factors threatening plant diversity globally apply for this area too. Wealth of information is slowly disappearing due to popollution, urbanization, industrialisation, dam constructions, means of communication etc. Polen diagrams from the area reveal early and widespread forest clearance, grazing and cultivation, even at high altitudes. The fire effects are 10.000 years old. Aridification of the climate has started here sometime between 1000 and 500 B.C. Recent information on the climatic variations shows that CO2 concentration in our atmosphere has touched the level of 390 ppm in 2010, and these developments are accepted as one of the greatest challenge for different plant taxa. It is causing noticeable effects on the growth and development as well as active ingredients of plants. Aromatic and medicinal plants are equally effected from these changes in particular high altitude plants. Such a change will lead to an increase in the biotic and abiotic stresses thus affecting the production of different compounds which in turn will effect their medicinal activity. There is an urgent need for important future research projects focussing on plant uses within communities living at higher altitudes, medical herbalism in different ethnic groups, local and neglected aromatic plants.