Abstract: The principle of ‘no significant harm’ as a way of addressing transboundary environmental challenges is both inadequately researched and inadequately implemented in many parts of the world. This paper addresses the questions: What is the nature of transboundary harm in the Anthropocene? Is the principle of no significant harm able to address current and pre-empt future transboundary harm in the field of water and environmental law? This special issue has focused on this principle in the arena of water law. This article integrates the findings in the context of a broader understanding of global harm in the Anthropocene. We draw 4 conclusions. First, conceptually harm is moving beyond direct inter-state harm between neighbouring countries to a multi-directional, multi-actor/multi-level harm, which is increasingly creeping and cumulative, with growing spatial and temporal characteristics. It thus requires moving beyond quibbling over what is ‘significant’ harm to recognize the climate emergency, the sixth biodiversity extinction, the huge damage to water systems and to realize that the threshold of ecosystem and human tolerance of damage are reducing rapidly.