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Introduction: Human activities can have many detrimental effects on large vertebrate species of East Africa, many of which are facing endangerment. As the human population continues to grow, this begs the question of how the effects of human activities can be mitigated for the purpose of wildlife conservation, as well as the drawbacks that should be considered in the implementation of various conservation practices.Methods: This paper reviews the major human activities that contribute to the endangerment of large vertebrate species in East Africa. Further, it addresses the primary conservation practices that are currently being implemented or considered to be implemented in the future. In providing a critical review of the evidence for the success of each practice, this paper puts forth suggestions for their optimal application. Findings: The primary human activities that contribute to large species’ endangerment are human land use, human-wildlife conflict, utilization of animals, depletion of prey, and climate change, which is exacerbated by the growing human population. The most common strategies to mitigate the effects of human activities are the designation of protected areas, optimization of land use, government intervention, efforts combatting global warming, and translocation of endangered species. However, each of the strategies are not without drawbacks, such as suboptimal establishment and implementation such as protected land not being in vertebrate hotspot areas, alienation of local communities through militarized conservation efforts, cost to local communities, diminished economic growth, and translocation practices being uninformed by genetic information.