The Amazon River, its huge basin, and the changes in biological processes that are rapidly occurring in this region are unquestionably of global significance. Hence, Global Change Biology is delighted to host a special thematic issue devoted to the Large-scale Biosphere–Atmosphere Experiment in Amazônia (LBA), which is a multinational, interdisciplinary research program led by Brazil. The goal of LBA is no less modest than its subject: to understand how Amazônia functions as a regional entity in the Earth system and how these functions are changing as a result of ongoing changes in land use. This compilation of 26 papers resulting from LBA-related research covers a broad range of topics: forest stocks of carbon (C) and nitrogen (N); fluxes of greenhouse gases and volatile organic compounds from vegetation, soils and wetlands; mapping and modeling land-use change, fire risk, and soil properties; measuring changes caused by logging, pasturing and cultivating; and new research approaches in meteorology to estimate nocturnal fluxes of C from forests and pastures. Some important new synthesis can be derived from these and other studies. The aboveground biomass of intact Amazonian forests appears to be a sink for atmospheric carbon dioxide (CO2), while the wetlands and soils are a net source of atmospheric methane (CH4) and nitrous oxide (N2O), respectively. Land-use change has, so far, had only a minor effect on basin-wide emissions of CH4 and N2O, but the net effect of deforestation and reforestation appears to be a significant net release of CO2 to the atmosphere. The sum of the 100-year global warming potentials (GWP) of these annual sources and sinks of CH4, N2O, and CO2 indicate that the Amazonian forest–river system currently may be nearly balanced in terms of the net GWP of these biogenic atmospheric gases. Of course, large uncertainties remain for these estimates, but the papers published here demonstrate tremendous progress, and also large remaining hurdles, in narrowing these uncertainties in our understanding of how Amazônia functions as a regional entity in the Earth system.