The residual risk of transfusion-transmitted viral infection in developed c
ountries is considered minimal or negligible. However, zero risk remains a
strong political objective. Genomic screening for HCV, HIV and HBV represen
ts a major advance, eliminating infectious blood donations collected during
the pre-seroconversion window period, rare cases of immunosilent infection
s and, possibly, a large spectrum of viral variants. In Western countries,
HCV RNA genomic screening started on pools of 16-400 plasma samples from in
dividual donations. Pooling may produce false-positive and false-negative r
esults. Individual donation testing is more suitable to blood screening but
requires multiplexing, automation, and affordable cost. Because donations
from individuals who are HBV DNA-negative/serologically positive, or those
apparently recovered from HCV infection, may remain infectious, it is unlik
ely that HBsAg, anti-HCV, and anti-HIV will be discontinued when genomic sc
reening is extended to all three viruses. HIV-I p24 antigen may prove redun
dant with HIV RNA screening. Anti-HTLV-l and HTLV-II will remain more effec
tive than genomic testing.