The 2018 report issued by a High-Level Panel on Water convened by the UN Secretary-General and the President of the World Bank, and consisting of 11 sitting heads of State and government, concluded that one of the main challenges facing global water governance is integration. Finding ways of integrating the different layers and areas of global water governance will, in turn, require institutional innovation. This article explores the potential of a well-tested yet largely under-studied approach to integration, namely that provided by the UNECE/WHO-Europe Protocol on Water and Health. It proposes that the Protocol be relied on both as an instrument and as a model that can be harnessed in four main ways: accession by a State or a regional organization (eg the EU) to the Protocol; amendment to give the Protocol a global scope; as a model framework for development, cooperation and foreign policy; as a model framework for the adoption of a contextualized instrument in another regional context.