Despite recent significant improvements in the viral safety of blood and blood products there remains a small risk of contamination mainly due to the existence of a window period before the appearance of antibodies. Nucleic acid amplification technologies (NAT) permit a direct detection of the viral genome itself with an extreme sensitivity and specificity, without depending anymore on the delayed appearance of antibodies. These technologies can be applied to detect most blood-borne viruses. However, the usefulness and strategies will largely depend on different features specific to the type of the virus, such as pathogenicity, prevalence of the infection, viral load during preseroconversion, doubling time of the virus and infectious dose. Many studies have already been conducted in different parts of the world, and the results proving the feasibility of the NAT screening are more than encouraging. However, some problems still remain to be solved in theroutine application of these technologies.