Hydrogen fuel cell (FC) vehicles are receiving increasing attention as a potential powerful technology to reduce the transportation sector's dependence on petroleum and substantially decrease emissions of greenhouse gases (GHGs) at the same time. This paper projects energy use and GHG emissions from different FC vehicle configurations and compares these values to the projected characteristics of similarly sized and performing gasoline and diesel fueled automobiles on a life cycle, well to wheels and cradle to grave basis. Our analysis suggests that for the next 20 or more years, new internal combustion engine (ICE) hybrid drive train vehicles can achieve similar levels of reduction in energy use and GHG emissions compared to hydrogen FC vehicles, if the hydrogen is derived from natural gas. The fleet impact of more fuel-efficient vehicles depends on the time it takes for new technology to (i) become competitive, (ii) increase its share of the new vehicles produced, and finally (iii) penetrate significantly into the vehicle fleet. Since the lead times for bringing improved ICE vehicle technology into production are the shortest, its impact on vehicle fleet energy use and emissions could be significant in 20–30 years, about half the time required for hydrogen FC vehicles to have a similar impact. Full emission reduction potential of FC vehicles can only be achieved when hydrogen is derived from zero or very low-carbon releasing production processes on a large scale—an option that further increases the impact leadtime. Thus, a comprehensive short- and long-term strategy for reducing automobile energy use and emissions should include both the continuous improvement of ICE vehicles and simultaneous research and development of hydrogen FC cars.