Forests and aquatic ecosystems are the basis for ecosystem services, which play a crucial role in people’s livelihoods, human well-being, and health. Some of the most relevant and challenging current health problems in Amazonia are associated with deforestation and degradation of terrestrial and aquatic ecosystems, including the risk of contracting infectious diseases, respiratory and cardiovascular problems caused by exposure to smoke from forest fires, and mercury (Hg) contamination due to mining and other deforestation and biomass burning practices. Emergent, re-emergent, and endemic infectious diseases in the Amazon have all been associated with environmental changes driven by rapid human population growth and/or socioeconomic transition. Yet the relationship between forest conversion and fragmentation and the incidence of infectious disease is complex, scale-dependent, and heavily modulated by socioecological feedbacks. Amazonia is also a region of exceptionally high (yet poorly known) diversity of viruses and viral hosts, exacerbating the risks of potential zoonotic spillovers. Another major environmental and public health concern in the Amazon basin is mercury contamination resulting from gold mining, hydropower dams, deforestation, and petroleum extraction. Not only are Amazon basin communities exposed to high Hg concentrations at risk of toxicological contamination, but environmental effects on water resources, fisheries and wildlife are seen throughout Amazonian ecosystems. As a result, communities with high levels of fish consumption present some of the world’s highest recorded Hg levels. The impact of fires are also a big concern, since they emit large quantities of particulate matter and other pollutants that degrade air quality and affect human health, especially among vulnerable groups in the Amazon. Here we demonstrate that environmental degradation is also a socio-economic issue, affecting the health of millions of Amazonians and compromises the quality of life and human health of future generations.