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This study assesses the evolution of major anthropogenic drivers of environmental impacts on Neotropical mangroves, the changes in the environmental pressures acting upon them, and the respective societal responses during the past 40 years. It reviews the impacts of new drivers, in particular those resulting from global climate change and the expansion in aquaculture and the effectiveness of local societal responses aimed at addressing them. Adaptation and mitigation actions are proposed to cope with the impacts and their socio-economic consequences for Latin America and Caribbean mangroves. By comparing the situation in Latin America and the Caribbean with other regions, the knowledge gaps and priority research needs are discussed to support delineating a preliminary unifying framework to address the environmental pressures affecting mangroves. This scenario necessarily includes the interaction of climate change with human interventions and their effects on ecosystem goods and services, as well as their respective adaptation and management options. Results show that drivers of environmental impacts have changed in the past 40 years, reducing the effectiveness of some important societal responses towards conservation and sustainable management with a great potential to increase rates of mangrove deforestation and conversion to human uses. Although efforts in conservation and restoration have contributed to decreasing pressure on these ecosystems, the coupling of old drivers, such as damming, with climate change, and the appearance of new drivers in the region, such as shrimp aquaculture, may eclipse the gains made through these conservation efforts. Despite the negative trend, we discuss some successful efforts to curb negative impacts of human activities on mangroves. We also recommend regional assessments based on primary sources in the representative mangrove-bearing countries throughout the continent to allow the upscaling of their experiences towards a regional response to the challenges facing Neotropical mangrove conservation and sustainable use.