The purpose of this work is to present a botanical, cultural and historical portrait of sesame use in Southwest Asia, from earliest time to the present. The crop's domestication and subsequent dispersal are reviewed from the archaeological literature and early texts. The introduction of sesame represents an agricultural innovation in Southwest Asia, since as a ‘tropical’ warm weather crop, sensitive to freezing temperatures, it is successfully grown in the region as a summer crop, by selecting cultivars that mature early. Its seeds are used as food and flavoring. The chief constituent of the seed is its prized oil, 45–60 % by weight that resists oxidative rancidity. It is used as a salad or cooking oil, an ingredient in cosmetics, in the manufacture of soaps, pharmaceuticals, and lubricants, and was formerly used as a lamp oil. The press cake remaining after the oil is expressed is a nutritious livestock meal. Information about medieval cultivation practices and evidence of its use in early centuries is extracted from historical manuscripts. Examples of sesame in art, myth, proverb and riddle from Southwest Asia provide a comparative, cross-cultural view of its service as a symbol. A survey of culinary, medicinal and linguistic data is presented. The status of its cultivation in the last century is represented by a rare look at practices in Armenia, Syria and Yemen.