We synthesized key findings from the Biological Dynamics of Forest Fragments Project, the world’s largest and longest-running experimental study of habitat fragmentation. Although initially designed to assess the influence of fragment area on Amazonian biotas, the project has yielded insights that go far beyond the original scope of the study. Results suggest that edge effects play a key role in fragment dynamics, that the matrix has a major influence on fragment connectivity and functioning, and that many Amazonian species avoid even small (Ͻ100-m–wide) clearings. The effects of fragmentation are highly eclectic, altering species richness and abundances, species invasions, forest dynamics, the trophic structure of communities, and a variety of ecological and ecosystem processes. Moreover, forest fragmentation appears to interact synergistically with ecological changes such as hunting, fires, and logging, collectively posing an even greater threat to the rainforest biota.