A conceptual framework is developed and used for improving the livelihood of Sub-Saharan communities faced with multiple stresses resulting from adverse environments, vector-transmitted diseases, and limited food. Ecosocial systems are the units for management. The accumulation of ecological, economic, and social capital is the objective of management, the reduction of maintenance costs is the key strategy, and technologies must satisfy ecological, economic, and social criteria. Interacting social system components are communities, facilitators, scientists, and political as well as administrative organizations. An adaptive approach to management allows flexibility in human and financial resource allocation and results in changes in knowledge and efficacy of management operations. The implementation strategy at two sites in Ethiopia relies on a two-stage procedure. In Stage 1, human and cattle health management set the conditions for development.In Stage 2, the ecosocial system is kept on a trajectory to enhanced ecological, economic, and social capital. In each stage, the assignment of responsibilities leads to four implementation phases. In Stage 1, successful precision targeting of tsetse and drug-based Trypanosoma spp. control increased the economic and social capital at the Luke site in southwestern Ethiopia but threatened the ecological capital because of overstocking and land degradation. In Stage 2, a women's group living in the outskirts of Addis Ababa (Ethiopia) transformed barren land into a horticultural enterprise to enhance ecosystem service provision, including production of horticultural goods, and increase soil fertility expressed by nutrients and water availability. This article reviews concepts on human livelihood improvement in Sub-Saharan Africa and identifies principles that became important during project execution.