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Domesticated in 8000–10,000 BP in northern China, proso millet (Panicum miliaceum L.) is the best adaptive rotational crop for semiarid central High Plains of the USA, where average annual precipitation is 356–407 mm. Proso millet has multiple benefits when consumed as human food. Proso millet is rich in minerals, dietary fiber, polyphenols, vitamins and proteins. It is gluten-free and therefore, ideal for the gluten intolerant people. Proso millet contains high lecithin which supports the neural health system. It is rich in vitamins (niacin, B-complex vitamins, folic acid), minerals (P, Ca, Zn, Fe) and essential amino acids (methionine and cysteine). It has a low glycemic index and reduces the risk of type-2 diabetes. Unfortunately, in the USA, it is mostly considered as bird feed, whereas it is mainly used as human food in many other countries. Besides human health benefits, proso millet has an impeccable environmental benefit. Proso millet possesses many unique characteristics (e.g., drought tolerance, short-growing season) which makes it a promising rotational crop for winter wheat-based dryland farming systems. Proso millet provides the most economical production system when used in a two years wheat/summer fallow cropping system in semiarid High Plains of the USA. It helps in controlling winter annual grass weeds, managing disease and insect pressure and preserving deep soil moisture for wheat. Proso millet can also be used as a rotational crop with corn or sorghum owing to its tolerance for atrazine, the primary herbicide used in corn and sorghum production systems. Proso millet certainly is a climate-smart, gluten-free, ancient, and small grain cereal, which is healthy to humans and the environment. The main challenge is to expand the proso millet market beyond bird feed into the human food industry. To overcome the challenge, unique proso millet varieties for human food and ready-to-use multiple food products must be developed. This requires successful collaboration among experts from diverse disciplines such as breeders, geneticists, food chemists and food industry partners.