Groundwater quality issues are becoming as important as groundwater quantity issues, making groundwater quality research a hot topic worldwide. With human activity intensifying in western China as a result of the West Development Program and the Silk Road economic belt project of China, groundwater quality in western China is deteriorating rapidly. This special issue of Exposure and Health promotes groundwater quality research to respond to these challenges. This introductory article details the challenges faced by contemporary groundwater quality researchers, and proposes ways to advance groundwater quality research in western China. The paper also introduces the articles that follow in this special issue. The key goal of this work is to encourage new and experienced scholars to engage with this field.