Despite measures to mitigate risk of transfusion-transmitted infections, emerging agents contribute to morbidity and mortality. We outline the epidemiology, risk mitigation strategies, and impact on patients for Zika virus, bacteria, Babesia, and cytomegalovirus. Nucleic acid testing of blood has reduced risk of Zika infection and reduced transfusion-transmitted risk of Babesia. Other collection and testing measures have reduced but not eliminated the risk of sepsis from bacterially contaminated blood components. Cytomegalovirus has almost been eliminated by high-efficiency leukoreduction, but residual transmissions are difficult to distinguish from community-acquired infections and additional antibody testing of blood may confer further safety of susceptible recipients.