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Although harm reduction practices have been increasingly adopted within health and social service systems globally over the last few decades, this process of institutionalization has not brought conceptual or theoretical clarity to the field of harm reduction. Instead, the growth of harm reduction practices within institutions has revealed the tension between grassroots approaches to harm reduction that focus on social activism and changing the underlying structural harms surrounding substance use, and the depoliticized institutional uses of harm reduction that focus on pragmatically managing individual substance use behaviour. In response to this tension and lack of theoretical clarity, the current paper proposes a critical pragmatist theoretical framework for harm reduction. To conclude, I reflect on some of the challenges for harm reduction within a shifting political landscape in North America. [Author discusses the Vancouver Area Network of Drug Users (VANDU) in some sections.]