Decision-makers at all levels of public health and transfusion medicine have always assessed the risks and benefits of their decisions. Decisions are usually guided by immediately available information and a significant amount of experience and judgment. For decisions concerning familiar situations and common problems, judgment and experience may work quite well, but this type of decision process can lack clarity and accountability. Public health challenges are changing as emerging diseases and expensive technologies complicate the decision-makers' task, confronting the decision-maker with new problems that include multiple potential solutions. Decisions regarding policies and adoption of technologies are particularly complex in transfusion medicine due to the scope of the field, implications for public health, and legal, regulatory and public expectations regarding blood safety. To assist decision-makers, quantitative risk assessment and cost-effectiveness analysis are now being more widely applied. This set of articles will introduce risk assessment and cost-effectiveness methodologies and discuss recent applications of these methods in transfusion medicine.