This review paper first discusses the needs for fundamental changes in the energy system for major efficiency improvements in terms of global resource limitation and sustainable development. Major improvement in energy efficiency of electric power plants and transportation vehicles is needed to enable the world to meet the energy demands at lower rate of energy consumption with corresponding reduction in pollutant and CO2 emissions. A brief overview will then be given on principle and advantages of different types of low-temperature and high-temperature fuel cells. Fuel cells are intrinsically much more energy-efficient, and could achieve as high as 70-80% system efficiency (including heat utilization) in electric power plants using solid oxide fuel cells (SOFC, versus the current efficiency of 30-37% via combustion), and 40-50% efficiency for transportation using proton-exchange membrane fuel cells (PEMFC) or solid oxide fuel cells (versus the current efficiency of 20-35% with internal combustion (IC) engines). The technical discussions will focus on fuel processing for fuel cell applications in the 21st century. The strategies and options of fuel processors depend on the type of fuel cells and applications. Among the low-temperature fuel cells, proton-exchange membrane fuel cells require H-2 as the fuel and thus nearly CO-free and sulfur-free gas feed must be produced from fuel processor. High-temperature fuel cells such as solid oxide fuel cells can use both CO and H2 as fuel, and thus fuel processing can be achieved in less steps. Hydrocarbon fuels and alcohol fuels can both be used as fuels for reforming on-site or on-board. Alcohol fuels have the advantages of being ultra-clean and sulfur-free and can be reformed at lower temperatures, but hydrocarbon fuels have the advantages of existing infrastructure of production and distribution and higher energy density. Further research and development on fuel processing are necessary for improved energy efficiency and reduced size of fuel processor. More effective ways for on-site or on-board deep removal of sulfur before and after fuel reforming, and more energy-efficient and stable catalysts and processes for reforming hydrocarbon fuels are necessary for both high-temperature and low-temperature fuel cells. In addition, more active and robust (non-pyrophoric) catalysts for water-gas-shift (WGS) reactions, more selective and active catalysts for preferential CO oxidation at lower temperature, more CO-tolerant anode catalysts would contribute significantly to development and implementation of low-temperature fuel cells, particularly proton-exchange membrane fuel cells. In addition, more work is required in the area of electrode catalysis.