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This chapter explores whether and how genomic resources can be protected by the communities from, or countries in which they are accessed. Specifically, it asks whether the Nagoya Protocol on Access and Benefit-Sharing can be an effective mechanism to reassure communities about the sharing of gene sequencing data. These questions are of particular importance to Indigenous peoples and local communities, as many have troubling historical experiences with colonization and associated natural resource exploitation. Many Indigenous and local communities (ILCs) live in developing countries, which are particularly sensitive to access and benefit-sharing (ABS) issues. Different but equally serious challenges exist for Indigenous peoples in developed countries like Canada, Australia, New Zealand and elsewhere. Until outcomes of implementation of the Nagoya Protocol are captured, Indigenous peoples and Local Communities (IPLCs) remain in a quandary as to how to protect digitized genetic resources within their territories or under their jurisdiction. To advance our understanding of legal and regulatory options, this chapter integrates normative and positive perspectives on the mechanisms for access and benefit-sharing in the age of digital biology.