Although the World Health Organization (WHO) has set targets for safe blood by 2012, Sub-Saharan Africa remains confronted with multi-factorial issues that compromise blood safety in most countries of the region. Some of these include the development and implementation of national policies for transfusion, the recruitment of voluntary and unpaid donors, proper screening of collected blood as well as a strategy for its rational use in a setting already plagued by a high prevalence of blood-borne agents, poverty, and sometimes organizational deficits. Furthermore, the organization of hemovigilance, as well as quality systems that could monitor transfusion practices is lacking in these settings. There is no funding and global improvement of blood safety has to be cheap to be feasible. Specific solutions for the African continent need to be developed and implemented. This paper examines the current status and difficulties of blood safety in Africa and reviews available data on transfusion medicine in the region.