During the past decade, technological advancements in the United States and Canada have led to rapid and intensive development of many unconventional natural gas plays (e.g., shale gas, tight sand gas, coal-bed methane), raising concerns about environmental impacts. Here, we summarize the current understanding of local and regional air quality impacts of natural gas extraction, production, and use. Air emissions from the natural gas life cycle include greenhouse gases, ozone precursors (volatile organic compounds and nitrogen oxides), air toxics, and particulates. National and state regulators primarily use generic emission inventories to assess the climate, air quality, and health impacts of natural gas systems. These inventories rely on limited, incomplete, and sometimes outdated emission factors and activity data, based on few measurements. We discuss case studies for specific air impacts grouped by natural gas life cycle segment, summarize the potential benefits of using natural gas over other fossil fuels, and examine national and state emission regulations pertaining to natural gas systems. Finally, we highlight specific gaps in scientific knowledge and suggest that substantial additional measurements of air emissions from the natural gas life cycle are essential to understanding the impacts and benefits of this resource.