The Minamata Convention on Mercury is a multilateral environmental agreement that obligates Parties to reduce or control sources of mercury pollution in order to protect human health and the environment. The Convention includes provisions on providing technical assistance and capacity building, particularly for developing countries and countries with economies in transition, to promote its effective implementation. Evaluating the effectiveness of the Convention (as required by Article 22) is a crucial component to ensure that it meets this objective. We describe an approach to measure effectiveness, which includes a suite of short-, medium-, and long-term metrics related to five major mercury control Articles in the Convention, as well as metrics derived from monitoring of mercury in the environment using select bioindicators, including people. The use of existing biotic Hg data will define spatial gradients (e.g., biological mercury hotspots), baselines to develop relevant temporal trends, and an ability to assess risk to taxa and human communities of greatest concern. We also recommend the development of a technical document that describes monitoring options for the Conference of Parties, to provide science-based standardized guidelines for collecting relevant monitoring information, as guided by Article 19.