The increasing population growth essentially requires more diverse food in the future. Pearl millet is a major source of diets that provides energy and nutrition for millions of people living in India and sub-Saharan Africa (SSA). Malnutrition prevalence is estimated at 2 billion people globally affected. Malnutrition is highly prevalent in India and SSA, and progress in addressing them through various recurrent costing interventions is slow. Biofortification is a nutrition-defined cost-competitive and sustainable approach for combating malnutrition among resource-poor households in low- and middle-income countries. Enhancing grain iron (Fe) and zinc (Zn) contents is prioritized for major staples including pearl millet as these two micronutrients are predominately deficient in human populations. HarvestPlus-supported biofortification pearl millet breeding globally accomplished significantly higher levels for Fe (80 mg kg−1) and Zn (60 mg kg−1) in germplasm, breeding populations, and hybrid parents using conventional breeding approaches. To date, 12 biofortified hybrids are released and are benefiting more than 120,000 households. Genetic gain for Fe and Zn is gradually increased (42 mg kg−1 to >75 mg kg−1 Fe; 30 mg kg−1 to 50 mg kg−1 Zn) and is higher than yield. Average levels of Fe (42 mg kg−1) and Zn (31 mg kg−1) in commercial hybrids and increased climate variability for pearl millet-growing areas will affect nutrition levels besides diminishing yield potential. Therefore, breeding for yield and nutrition should go hand in hand with mainstreaming nutrition. The use of biofortified cytoplasmic male sterile (CMS) lines and restorers, breeding pipelines in crossing, and application of improved breeding methods through precision phenotyping, genomic selection, and speed breeding options can expedite mainstreaming progress in pearl millet. Bioavailability studies confirm the improved human health significance of biofortified varieties and hybrids. Accelerated public-private partnership is essential in achieving higher nutrition in competitively yielding hybrids. Consumer preferences for nutritious millet grains have increased, thus prospecting nutrient-dense varieties for improved human nutrition in India and SSA.