Lack of blood is common in SSA but quantification of the overall shortfall is hampered by a lack of evidence-based targets for blood collection. Despite recommendations that all blood donors should be voluntary and non-remunerated, replacement donors are common throughout sub-Saharan Africa (SSA). Voluntary donors are generally recruited through centralised systems whereas replacement donors are recruited by families and donate through hospitals. Blood from a centralised service is more expensive than from a hospital-based service due to the higher costs of donor recruitment, quality assurance processes and the maintenance of distribution networks. Information about the contribution of replacement donors to the blood supply is scanty and inconsistent but it is likely that they currently provide over half of the blood in SSA. WHO's guidelines for transfusion services deal exclusively with voluntary donors and neglect the substantial contribution made by replacement donors. Examples of how the supply and quality of blood from the replacement donors can be improved have been published but need to be evaluated and disseminated. Political will and open-mindedness to innovative ways to improve supply and safety of blood from all types of donors are essential to promote more evidence-based approaches to blood transfusion practice in low-income countries.