The contention that alcohol and other drug (AOD) use is mediated in a social context is the principal condition of a social science of harm reduction (Rhodes, 2009, pp. 193-195). It is equally implicit in all 'social explanations' of the problems sometimes associated with this use. Indeed, it seems that the very promise of a social science of drugs is beholden to the conviction that social forces intervene somehow in the course of AOD consumption, changing it in ways that are amenable to empirical inquiry. What then, may be said to constitute a 'social explanation' of AOD use, including the problems associated with this use and the most effective ways of reducing them? And what, more directly, does it mean to say that cultures and social contexts mediate AOD use? The group of essays assembled for this 'special focus' address these questions in highly original ways, drawing from the theoretical, empirical and methodological resources furnished in contemporary studies of science, technology and society (STS), and Actor-Network Theory (ANT) more directly. Each contribution follows ANT's lead in suggesting that established epistemological distinctions like subject/ object, structure/agent, nature/culture and human/nonhuman impede, rather than facilitate, the work of producing empirically nuanced accounts of phenomena like AOD use (Wilton & Moreno, 2012, pp. 99-101). While the practice of social science inquiry absent, after or beyond the subject/object dyad may appear almost perverse, ANT and STS each proceed from the claim that novel ontological investments are urgently required in light of the imbrications of science, technology, media, communication and power that characterise 'late' modernity (Latour, 2005; Mol, 2010). Each contribution to this 'special focus' provides a sketch of what a social science of harm reduction might look like in the wake of such ontological novelty.