The transfusion‐transmitted infection (TTI) risk of pathogens for which nucleic acid testing (NAT) has been implemented is now insubstantial compared to other hazards of transfusion. Minimizing the TTI risk of non‐tested pathogens is a goal of pathogen inactivation (PI); in particular, the interdiction of emerging pathogens is a major selling point. Incidental to PI is the possibility of eliminating certain patient‐oriented procedures, e.g. selectively screening for cytomegalovirus (CMV) or irradiating to prevent transfusion‐associated graft‐versus‐host disease (TA‐GVHD). Do NAT and PI introduce new hazards? Perhaps. The product‐oriented elements of ‘SQuIPP’– Safety, Quality, Identity, Purity and Potency – are interdependent in positive and negative ways, and every intervention, including NAT and PI, requires time and money. Time has a special impact on the quality and availability of labile products such as granulocytes and platelets. Money spent on one intervention is unavailable for any other, and is not necessarily allocated to yield the best overall cost per quality adjusted life year (cost/QALY) or similar measure. Thus, current debate often focuses on NAT vs. PI. The ‘right’ answer likely depends on circumstances; a recent Chikungunya epidemic in La Réunion provoked rapid deployment of PI to ensure a sufficient, local platelet inventory, but the quality of PI‐treated products is a matter of ongoing investigation. For the future, we should dare to imagine, and dare to insist on, better performance for lower cost in all safety interventions. Information technology (IT) and automation have probably shown the greatest cost/performance improvements in recent years, especially as recording and processing approach the molecular level. A rational next step is to acknowledge that DNA and RNA are themselves data storage media, which await better techniques for reading (and editing). The issue will not be how little we can test, but how well we can handle the vast data available in every donor sample. In a world of nucleic acid surveillance (NAS), ethics and privacy will be at the forefront of donor‐oriented considerations. As for products manufactured from donated blood, today’s photochemistry may be the beginning of a new wave. Now, we disable nucleic acid replication. In the future, we might regulate apoptosis or modify antigens. Product optimization (PO), starting with rational donor selection criteria, will proceed with manufacturing steps best suited to a particular patient’s circumstances, e.g. the platelets given for an acute haemorrhage may very well differ from those given solely for prophylaxis. What is least likely to harm should be replaced by what is most likely to help.