Natural gas is the dominant feedstock for large-scale production of many chemicals, such as methanol and synthetic fuels, either using the TIGAS process to produce gasoline or using Fischer-Tropsch synthesis to produce diesel. Significant research has gone into the development of processes that convert natural gas directly into the end product. However, the most economical route today, and in the years to come, is a process in two stages with synthesis gas production as the first step. The most capital- and energy-intensive aspect of producing synthetic fuels and chemicals is synthesis gas production. This paper outlines and compares key technologies for large-scale production of synthesis gas. We find that auto-thermal reforming at a low steam-to-carbon ratio is the most economic and efficient technology for synthesis gas production in plants both for producing methanol and synthetic fuels.