Biofuels are by now a well-established component of the liquid fuels market and will continue to grow in importance for both economic and environmental reasons. To date, all commercial approaches to biofuels involve photosynthetic capture of solar radiation and conversion to reduced carbon; however, the low efficiency inherent to photosynthetic systems presents significant challenges to scaling. In 2009, the US Department of Energy (DOE) Advanced Research Projects Agency-Energy (ARPA-E) created the Electrofuels program to explore the potential of nonphotosynthetic autotrophic organisms for the conversion of durable forms of energy to energy-dense, infrastructure-compatible liquid fuels. The Electrofuels approach expands the boundaries of traditional biofuels and could offer dramatically higher conversion efficiencies while providing significant reductions in requirements for both arable land and water relative to photosynthetic approaches. The projects funded under the Electrofuels program tap the enormous and largely unexplored diversity of the natural world, and may offer routes to advanced biofuels that are significantly more efficient, scalable and feedstock-flexible than routes based on photosynthesis. Here, we describe the rationale for the creation of the Electrofuels program, and outline the challenges and opportunities afforded by chemolithoautotrophic approaches to liquid fuels.