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Deforestation in Central America’s rain forests is a growing problem that is typically attributed to the expansion of the agricultural frontier, yet little is known about the historical drivers of migration, settlement and forest loss. This chapter presents the results from a scoping study conducted in northeastern Nicaragua in the municipality of Siuna. Siuna has a rich history of colonization and nearly the entire municipality shares jurisdiction with the Bosawas Biosphere Reserve. The study landscape is also part of the Nicaragua-Honduras Sentinel Landscape, a multi-year collaborative research program site of the CGIAR Consortium. This chapter highlights the importance of resource extraction, natural disasters, policies and politics, economics, and the role of local and global conflicts and their aftermaths in influencing human migration and settlement patterns. We also discuss important conservation management and human rights issues related to the history of settlement within Siuna and the Reserve.