The recent increase in funding for diseases endemic in resource-poor countries has led to a progressive rise in the number of trials conducted in Africa for product development purposes or to answer important questions on reduction of disease burden. This causes an increasing demand for data safety monitoring boards (DSMBs) within Africa, where there is currently a shortage of appropriately skilled people. To address this, and in line with capacity-building efforts directed at improved quality research, AMANET invited the authors to create a curriculum and to train selected Africans with the skills required for members of DSMBs. Based on experience, the facilitators made an overview of clinical trial designs, a comprehensive review of data safety monitoring guidelines and other relevant DSMB governance issues. The wealth of guidelines and recommendations available for establishing and running DSMBs focus mainly on trials set in developed countries. The authors drew from these guidelines a practical summary of those relevant for Africa. This interactive process enabled recommendation of a straightforward set of principles to guide the establishment of DSMBs in Africa, which strike that essential balance between protecting trial participants and allowing investigators to answer their scientific questions.