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Sesame (Sesamum indicum L.) is an annual plant whose seeds are purported to be one of the oldest oilseeds used by humans. Although originating in Africa and India, this plant currently is cultivated in diverse regions worldwide from semiarid tropics to temperate areas. This edible seed oil has many routine and diverse uses in food preparation and cooking, and the dehulled seed is included in the preparation of numerous food products, condiments, and confectionaries, imparting a distinctive savory, nutty, roasted flavor. Sesame has a long history of use in traditional medicines for treatment of wounds, asthma, blurred vision, abdominal pain and ulcers, toothaches and gum disease, and migraine, to name a few. More recently, sesame constituents have demonstrated antioxidant and anti-inflammatory properties that may alleviate conditions such as atherosclerosis, diabetes, hypertension, and pain. The current narrative summarizes human studies evaluating sesame seeds, oil, and constituents for improving diverse human disorders, and provides suggestions for future research.