Worldwide safety of blood has been positively impacted by technological, economic and social improvements; nevertheless, growing socio-political changes of contemporary society together with environmental changes challenge the practice of blood transfusion with a continuous source of unforeseeable threats with the emergence and re-emergence of blood-borne pathogens. Pathogen reduction (PR) is a proactive strategy to mitigate the risk of transfusion-transmitted infections. PR technologies for the treatment of single plasma units and platelet concentrates are commercially available and have been successfully implemented in more than 2 dozen countries worldwide. Ideally, all labile blood components should be PR treated to ensure a safe and sustainable blood supply in accordance with regional transfusion best practices. Recently, a device (Mirasol® Pathogen Reduction Technology System) for PR treatment of whole blood using riboflavin and UV light has received CE marking, a significant step forward in realising blood safety where WB transfusion is the norm, such as in sub-Saharan Africa and in far-forward combat situations. There is also keen interest in the ability to derive components from Mirasol®-treated whole blood, as it is seen as a more efficient and economical means to implement universal PR in the blood centre environment than treatment of components with different PR systems.