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This chapter evaluates the potential for the governance of access and benefit-sharing in Canada through the lens of different layers of government: federal, provincial, territorial and Indigenous. The emphasis of the chapter is on how the nation-to-nation approach could be an effective way to integrate Indigenous peoples’ claim to genetic resources (GR) and their traditional knowledge (TK) as aspects of their self-determination. A nation-to-nation approach recognizes Indigenous peoples as stakeholders in access and benefit-sharing (ABS) in ways that advance the pursuit of justice and reconciliation in Canada. With the backdrop of ongoing policy initiatives and multifaceted attempts at renewing Canadian-Indigenous relations, the chapter underscores the federal government’s role in driving the charge. It will also require a commitment on the part of provincial governments, and overall political will across Canada, to draw in Indigenous peoples as genuine partners in order to fully integrate their legal traditions. Before Canada can implement the Nagoya Protocol, and any other ABS vision for that matter, all governments need to take the nation-to-nation mantra seriously and to articulate the legal status of GR and TK in Canada.