Pearl millet is a small-seeded staple crop in arid and semi-arid regions of Africa and Asia. It is the crop of choice in the hottest and driest climates where other cereals do not grow well and is considered a future climate-smart cereal. This underutilized cereal provides nutritional and food security to millions of people. It is also used as animal feed, fuel, and fodder as well as in brewing. The gluten-free grains of this cereal are rich sources of fats, proteins, carbohydrates, minerals, especially iron and zinc, and phenolics with health-promoting properties. Pearl millet also has industrial uses in the production of bioenergy, biodegradable products, bio-coagulants, and construction materials, and in tissue engineering. Pearl millet hybrids have gained considerable popularity among Indian farmers, resulting in a significant increase in production yields. However, pearl millet production in Africa is primarily dependent on traditional landraces with limited acceptance of improved open-pollinated varieties and hybrids. Consequently, no significant increase in pearl millet production has been achieved over the past few decades. Despite its inherent resilience against poor climates, this staple crop faces a complex array of abiotic and biotic stresses in its production areas, which is exacerbated by ongoing climate change. Furthermore, certain anti-nutritional traits impede its overall nutritional value and effective utilization. Hence, improving pearl millet is a continuous and significant challenge for plant breeders and biotechnologists.