Synthetic biology promises to leverage engineering principles to enable model-based design of genetic circuits. To be successful, advancements are needed in both experimental and computational methods to support this new approach. This paper focuses on the progress on the computational side, the remaining challenges, and the road ahead. While much work remains to be done for computational methods to truly have impact on experimental synthetic biology, collaborations between computational and experimental synthetic biologists have the potential for tremendous impact in the areas of health, energy, and the environment.