The ancient grain proso millet (Panicum miliaceum L.) is acknowledged for its tolerance to climatic fluctuations, presenting considerable potential to address food and nutritional shortages. Despite its limited use, it is highly regarded for its capacity to flourish in marginal soils, short growth duration of 65–75 days, minimal fertilizer and water needs, and intrinsic tolerance to biotic and abiotic stressors. Proso millet, traditionally farmed in Asia and Eastern Europe and now grown globally, is genetically enriched in carbohydrates, proteins, important minerals, such as iron and magnesium, and dietary fiber. Its gluten-free composition and low glycemic index render it especially advantageous for health-conscious diets and management of metabolic diseases, including diabetes. This chapter offers a comprehensive and interdisciplinary analysis of proso millet, including its botanical characteristics, historical origins, domestication, traditional uses, and cultural importance in different regions. It details cultivation methods, soil and climatic requirements, issues in pest and disease control, and the use of genomics, molecular breeding technologies, and value-added products. This chapter emphasizes the need to enhance research and breeding initiatives to increase productivity and incorporate it into mainstream agriculture. Through targeted initiatives, proso millet can address global challenges such as food insecurity, hunger, and climate change, positioning it as a sustainable crop for the future.