Infectious agents, including viruses, bacteria and parasites, can be transmitted via human blood and blood products. Of greatest importance are viruses such as human immunodeficiency virus types 1 and 2 (HIV-1/2), hepatitis B virus (HBV), and hepatitis C virus (HCV), followed by other viruses such as cytomegalovirus (CMV) and human parvovirus B19. Viruses such as hepatitis G virus and TT virus can also be transmitted via blood products, but their pathogenicity is still unclear. Bacteria, including Treponema pallidum and Yersinia enterocolitica and parasites such as Plasmodium species can also be transmitted from donors to recipients. Furthermore, the threat of newly emerging pathogens that can affect the blood safety, such as the variant Creutzfeld-Jakob Disease, is always present. The measures to reduce the risks of transfusion-transmitted infection within the last 20 years, such as donor selection and testing donated blood for various infectious agents, have had a remarkable impact on the safety of blood supply. Nevertheless, the public expectation of absolute blood safety continues to exert pressure to eliminate the remaining risks. The recent introduction of molecular biology techniques combined with viral inactivation methods is directed to get this goal.