The scale of human pressures on marine ecosystems gradually increased from local to global effects during the last centuries. Global warming, sea level rise and trans-oceanic spread of alien species are now or will be major drivers of ecological change in the Wadden Sea. Eutrophication may rank as a super-regional effect as the organic matter turnover in the Wadden Sea is driven by import from the North Sea. These effects will not necessarily be uniform across the entire Wadden Sea. A major challenge will be to understand the interactions between global factors with local conditions, both changed by human interference. A conceptual understanding of factors leading to regional differences within the Wadden Sea is only slowly evolving. Based on our understanding of the eutrophication process and a regional comparison of the eutrophication status of the Wadden Sea we propose that wider tidal basins (with a large distance between barrier islands and the mainland) generally have a lower eutrophication status than narrower tidal basins (with a short distance between barrier islands and mainland). This may be explained by a "dilution" of the imported organic matter in wider tidal basins. The interactions between global and super-regional effects on local ecological developments in the Wadden Sea will be complex and pose a major challenge to science, Wadden Sea management and the assessment of ecosystem health as required by EU legislation. The implications of integrating a North Sea view into Wadden Sea management are discussed and we conclude that the river basin approach of the EU Water Framework Directive is not appropriate for the Wadden Sea. © 2012 Elsevier Ltd.