Fugitive emissions from natural gas are an important source of methane to the atmosphere. A great deal of progress has been made in recent years on the quantification and characterization of methane emissions from all parts of the natural gas supply chain, yet distribution and end-use remain arguably the least well-understood emitting sector. This presentation will describe our project in Boston to quantify methane emissions from natural gas using an atmospheric measurement and modeling framework. We found that the fractional loss rate of all natural gas delivered to the Boston urban region was two to three times larger than that predicted by inventory methodologies and industry reports. More recent studies have found similar results for other cities, suggesting natural-gas-consuming regions, generally, may be larger sources of methane to the atmosphere than is currently estimated and represent areas of significant resource loss. However, studies focused on identifying the most important mechanisms for natural gas loss in urban areas (e.g. pipeline leaks versus end-use leaks) have yet to deliver actionable results. To conclude, I will discuss the fundamental measurement, engineering, and policy challenges for accurately characterizing and subsequently reducing emissions from natural gas distribution and end-use.