The viral safety of biologicals, either human blood derivatives or animal products or recombinant proteins issued from biotechnology, relies on the quality of the starting material, the manufacturing process and, if necessary, the control of the final product. The quality of the starting material is highly guaranteed for blood derivatives due to the individual screening for specific markers (antigens, genome, antibodies) for major blood borne viruses such as hepatitis B and C viruses (HBV, HCV) and human immunodeficiency virus (HIV). It can be reinforced by the detection through amplification procedures (polymerase chain reaction) in the plasma pool of genomes from viruses that have been implicated in contaminations of blood derivatives in the past (parvovirus B19, hepatitis A virus). The association in the manufacturing process of different steps dedicated to purification of plasma proteins (partitioning), virus inactivation (solvent/detergent treatment, heat inactivation) or specific procedures allowing virus removal (nanofiltration) allows to reduce the viral risk very efficiently. The validation studies using scaled down systems and model viruses allow to evaluate the virus safety of any product quantitatively. The aim of these procedures is to guarantee the lack of infectivity due to any virus, either known or unknown.