This article examines the opportunities for using several forms of modern biotechnology to improve orphan crops in developing countries. These crops, including tef, millets, cowpea, and indigenous vegetables, fruits, roots, and tubers, tend to be locally important, but receive little public or private investment. Recent advances in the fields of genetics and genomics provide a more unified understanding of the biology of plants. We summarize some important ways in which genetic technologies can be harnessed for orphan crops and provide examples of potential genetic and genomics research that is likely to benefit poor regions. Finally, we suggest policies that could help create incentives for application of advanced science to orphan crops.