Sorghum (Sorghum bicolor (L.) Moench) is a staple food grain in many semi-arid and tropical areas of the world, especially in sub-Saharan Africa and some parts of Asia. In a breeding program for sorghum quality traits, the breeder needs to understand the nutritional and grain quality traits of the crop and the target environments. Therefore, the objective of the article is to review the major nutritional and antinutritional factors of sorghum grain concerning seed protein, starch, and phenolic compounds in line with their breeding and genetics perspectives. The sorghum grain major nutritional quality traits such as content and digestibility of protein and starch, nutritional and antinutritional factors regarding phenolic compounds with there corresponding genetics and breeding perspectives were discussed in this article. Moreover, genotypes and mutants, which have superior grain nutritional quality traits and QTLs and genes that govern quality traits such as lysin, amylose/amylopectin, and tannin content and also inheritance pattern were discussed.