Global greenhouse gas emissions, combined with local deforestation and forest degradation, are pushing the Amazonian system closer to a tipping point. A large-scale Amazon tipping point may trigger the collapse of most forests and consequently: (1) accelerate global warming, hindering efforts to achieve the goals of the Paris Agreement; (2) reduce moisture flow across South America, threatening water security for basic socioeconomic activities, such as agriculture; (3) increase temperatures across the Amazon region that may become unbearable for humans living in urban and rural areas; (4) cause mass species extinctions; and (5) compromise the biological and cultural assets that represent key solutions to the current and future challenges of humanity. Synergies between disturbances may cause unexpected tipping behaviour, even in forest regions previously considered as resilient to climate change, such as the central or western Amazon.