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Sorghum grain provides an important calorific source for millions of people living in developing countries and is a principal animal feed and source of gluten-free flour for the livestock and food processing industries of developed nations. A versatile grain, sorghum is also widely utilized in the production of alcoholic beverages in countries such as China and several countries in sub-Saharan Africa, where the liquor baijiu and beer are a major end-use, respectively. Renowned as a hardy crop, sorghum is relatively drought tolerant and can be grown on marginal lands and is adaptable to a wide range of environmental conditions, giving this species particular advantages over other cereals. Despite its inherent benefits, sorghum has not proven to be a major alternative to the other notable cereals such as wheat and maize, due to significant problems concerning the low amount of specific essential amino acids, for example, lysine, lower protein content, lower starch digestibility, and smaller grain size, which has implications for the traits mentioned above as well as acting as an impediment to efficient grain handling in cereal-processing industries. The challenges in enhancing sorghum grain quality are not insurmountable and great strides have already been achieved in a relatively short time via scientific breeding to enhance grain yield and provide abiotic and biotic stress resistance. As the sorghum market has matured, demand for higher quality grain, whether for alcohol production or animal and human consumption, is increasing. Although yield and disease resistance are still the primary focus of breeders, advances in genomics, online bioinformatic data repositories, high-throughput phenotypic screening such as near-infrared reflectance (NIR), and the increasing affordability of next-generation sequencing, have allowed breeders to incorporate improved grain quality parameters into their programs. This chapter elaborates recent advances in genomics that have provided researchers with the tools to solve several of the issues surrounding grain quality in sorghum as well as future directions for experimentation.