Achieving the CO2 reduction targets for 2050 requires extensive measures being undertaken in all sectors. In contrast to energy generation, the transport sector has not yet been able to achieve a substantive reduction in CO2 emissions. Measures for the ever more pressing reduction in CO2 emissions from transportation include the increased use of electric vehicles powered by batteries or fuel cells. The use of fuel cells requires the production of hydrogen and the establishment of a corresponding hydrogen production system and associated infrastructure. Synthetic fuels made using carbon dioxide and sustainably-produced hydrogen can be used in the existing infrastructure and will reach the extant vehicle fleet in the medium term. All three options require a major expansion of the generation capacities for renewable electricity. Moreover, various options for road freight transport with light duty vehicles (LDVs) and heavy duty vehicles (HDVs) are analyzed and compared. In addition to efficiency throughout the entire value chain, well-to-wheel efficiency and also other aspects play an important role in this comparison. These include: (a) the possibility of large-scale energy storage in the sense of so-called ‘sector coupling’, which is offered only by hydrogen and synthetic energy sources; (b) the use of the existing fueling station infrastructure and the applicability of the new technology on the existing fleet; (c) fulfilling the power and range requirements of the long-distance road transport.