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Over the last five decades, the Athabasca River Basin in Alberta, Canada, has been subjected to a wide range of environmental stressors from diverse human developments. This has resulted in an escalation of government, academic, industry and community-based monitoring and research efforts. However, despite all the attention received, a comprehensive synthesis of what has been studied is lacking, in particular, in relation to the efforts examining single versus multiple stressors. Based on a systematic literature review, we found 386 publications from 1969 to 2018 on the Athabasca River focusing on single stressors (68.4%) compared to multiple stressors (31.6%). There was a significant shift in the focus of studies between the 1990s and present from assessing threats of pulp and paper developments to those related to oil sands activities, with studies most predominantly addressing chemical stressors. Despite these efforts, there remain significant knowledge gaps regarding the cumulative effects of multiple stressors, particularly on biological and ecological endpoints. Correspondingly, a wide range of contradictory conclusions were reported regarding the ecological, regulatory and societal significance of the reported environmental impacts, highlighting both the complexity and often lack of standardization of approaches used. This emphasizes the need for improved integration of monitoring and research activities that are hypothesis driven, have clear objectives, and are better aligned with environmental management processes and decisions. (c) 2018 Elsevier B.V. All rights reserved.