Transfusion has been tainted with the risk of contracting an infection – often severe – and fears about this risk are still prevailing, in sharp contrast with the actual risk in Western countries. Those actual risks are rather immunological, technical (overload) or metabolic. Meanwhile, in developing countries and particularly in Africa, transfusion transmitted infections (TTIs) are still frequent, because of both the scarcity of volunteer blood donors and resources and the high incidence and prevalence of infections. Global safety of blood components has been declared as a goal to be attained everywhere by the World Heath Organization (WHO). However, this challenge is difficult to meet because of several intricate factors, of which the emergence of infectious agents, low income and breaches in sanitation and hygiene. This review aims at encompassing the situation of TTIs in different settings and means that can be deployed to improve the situation where this can possibly be.