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The impact of invasive species on native biodiversity is increasing worldwide. Mammalian invaders are formidable ecological and economic threats, and tree squirrels are models of such challenges. We review the worldwide distribution of tree squirrel introductions and detail their nearly universal success. The biological characteristics of tree squirrels that enable success as invasive species are: high reproductive potential, high vagility, diverse food habits, ability to construct nests, and plasticity in human-impacted landscapes. We document costs and benefits of tree squirrel introductions, and discuss existing management strategies planned for some species. We focus on an introduced population of Mexican red-bellied squirrels (Sciurus aureogaster) found in Biscayne National Park, Florida, United States. Originally introduced to Elliot Key in 1938, the population expanded until Hurricane Andrew in 1992. Thought to be extirpated, recent sightings initiated a project to assess status and distribution within the Park. A field study has provided valuable information on potential and realized impacts that the squirrel population has on the native ecosystem that includes several species of conservation concern. Management strategies for Mexican red-bellied squirrels can be formed after research to develop prudent and effective means to meet the challenges that result from control measures to deal with this exotic species.