The existence, magnitude and duration of a supposed “CO2 fertilization” effect in tropical forests remains largely undetermined, despite being suggested for nearly 20 years as a key knowledge gap for understanding the future resilience o Amazonian forests and its impact on the global carbon cycle. Reducing this uncertainty is critical for assessing the future of the Amazon region as well as its vulnerability to climate change. The AmazonFACE (Free-Air CO2 Enrichment) research program is an experiment of unprecedented scope in an old-growth Amazon forest near Manaus, Brazil – the first of its kind in tropical forest. The experimental treatment will simulate an atmospheric CO2 concentration [CO2] of the future in order to address the question: “How will rising atmospheric CO2 affect the resilience of the Amazon forest, the biodiversity it harbors, and the ecosystem services it provides, in light of projected climatic changes?” AmazonFACE is divided into three phases: (I) pre-experimental ecological characterization of the research site; (II) pilot experiment comprised of two 30-m diameter plots, with one treatment plot maintained at elevated [CO2] (ambient +200 ppmv), and the other control plot at ambient [CO2]; and (III) a fully-replicated long-term experiment comprised of four pairs of control/treatment FACE plots maintained for 10 years. A team of scientists from Brazil, USA, Australia and Europe will employ state-of-the-art methods to study the forest inside these plots in terms of carbon metabolism and cycling, water use, nutrient cycling, forest community composition, and interactions with environmental stressors. All project phases also encompass ecosystem-modeling activities in a way such that models provide hypothesis to be verified in the experiment, which in turn will feed models to ultimately produce more accurate projections of the environment. Resulting datasets and analyses will be a valuable resource for a broad community, especially ecosystem and climate modelers, and policy-makers.