Natural gas is typically considered to be the cleaner-burning fossil fuel that could play an important role within a restricted carbon budget. While natural gas emits less CO2 when burned than other fossil fuels, its main constituent is methane, which has a much stronger climate forcing impact than CO2 in the short term. Estimates of methane emissions in the natural gas supply chain have been the subject of much controversy, due to uncertainties associated with estimation methods, data quality, and assumptions used. This Perspective presents a comprehensive compilation of estimated CO2 and methane emissions across the global natural gas supply chain, with the aim of providing a balanced insight for academia, industry, and policy makers by summarizing the reported data, locating the areas of major uncertainty, and identifying where further work is needed to reduce or remove this uncertainty. Overall, the range of documented estimates of methane emissions across the supply chain is vast among an aggregation of different geological formations, technologies, plant age, gas composition, and regional regulation, not to mention differences in estimation methods. Estimates of combined methane and CO2 emissions ranged from 2 to 42 g CO2 eq/MJ HHV, while methane-only emissions ranged from 0.2% to 10% of produced methane. The methane emissions at the extraction stage are the most contentious issue, with limited data available but potentially large impacts associated with well completions for unconventional gas, liquids unloading, and also the transmission stage. From the range of literature estimates, a constrained range of emissions was estimated that reflects the most recent and reliable estimates: total supply chain GHG emissions were estimated to be between 3.6 and 42.4 g CO2 eq/MJ HHV, with a central estimate of 10.5. The presence of “super emitters”, a small number of facilities or equipment that cause extremely high emissions, is found across all supply chain stages creating a highly skewed emissions distribution. However, various new technologies, mitigation and maintenance approaches, and legislation are driving significant reductions in methane leakage across the natural gas supply chain.