Attributable mortality due to transfusion-associated graft-versus-host disease (TA-GVHD) in contrary to the reaction occurring after transplantations has been estimated to be more than 95%. This type of reaction may occur not only in immunocompromised patients but also in patients without immune deficits. Because there is currently no available treatment for TA-GVHD and very high mortality the goal has been to reduce the likelihood of occurrence in recipients at risk of TA-GVHD. The removal of all lymphocytes from blood components is very difficult and highly impracticable. Much easier way to neutralize lymphocytes presents irreversible injury of their genetic material. It can be achieved by using ionizing irradiation (gamma- or X-ray) or pathogen reduction technologies (PRT). PRT use ultraviolet light with or without photosensitizers. Since PRT cause damage to nucleic acids, they also have potential to inactivate lymphocytes T, making them unable to proliferate, engraft and cause TA-GVHD. Transmission of infections, particularly those not routinely tested in blood components, presents still significant problem in spite of constant improvement of methods applied for donor qualification, blood testing and preparation techniques. PRT have a goal to minimize the risk of transfusion-related pathogen transmission. PRT are equally effective in TA-GVHD prophylaxis as gamma irradiation and according to current guidelines may be applied alternatively. However PRT have advantage over gamma irradiation because they additionally decrease the risk of pathogen transmission via platelet concentrate transfusion and limit proinflammatory cytokine production as well as lymphocyte activation in blood components.