Abstract C4 photosynthesis drives productivity in several major food crops and bioenergy grasses, including maize (Zea mays), sugarcane (Saccharum officinarum), sorghum (Sorghum bicolor), Miscanthus x giganteus, and switchgrass (Panicum virgatum). Gains in productivity associated with C4 photosynthesis include improved water and nitrogen use efficiencies. Thus, engineering C4 traits into C3 crops is an attractive target for crop improvement. However, the lack of a small, rapid cycling genetic model system to study C4 photosynthesis has limited progress in dissecting the regulatory networks underlying the C4 syndrome. Setaria viridis is a member of the Panicoideae clade and is a close relative of several major feed, fuel, and bioenergy grasses. It is a true diploid with a relatively small genome of ~510 Mb. Its short stature, simple growth requirements, and rapid life cycle will greatly facilitate genetic studies of the C4 grasses. Importantly, S. viridis uses an NADP-malic enzyme subtype C4 photosynthetic system to fix carbon and therefore is a potentially powerful model system for dissecting C4 photosynthesis. Here, we summarize some of the recent advances that promise greatly to accelerate the use of S. viridis as a genetic system. These include our recent successful efforts at regenerating plants from seed callus, establishing a transient transformation system, and developing stable transformation.