Sorghum has a relatively small diploid genome, and retains much of the chromosomal structure and organization of its common ancestor. It also has multiple origins of domestication in different regions of Africa, resulting in a highly diverse germplasm well adapted to drought and other challenging environmental conditions. This makes sorghum ideal for dissecting the architectures of complex yet desirable traits. This chapter discusses what we know about the evolution and structure of the sorghum genome, the impact of domestication and the genetic architecture of key traits such as C4 photosynthesis and drought tolerance.