Donor-derived infectious diseases are infections that are present in an organ donor and have the potential to be transmitted to at least 1 transplant recipient. Several recent transmissions have been covered by the lay media and in the medical literature, including a recent transmission of HIV and hepatitis C virus from 1 donor to 4 recipients. These reports have highlighted the importance and clinical impact of this rare complication of organ transplantation. Donor-derived infectious diseases appear to complicate less than 1% of all transplant procedures, but, when a transmission occurs, significant morbidity and mortality can occur. A number of guidelines and policies define the optimal screening of organ donors to prevent the transmission of infectious diseases. Unfortunately, there are significant limitations in our screening methods, and only some pathogens are screened for routinely. The regulatory framework related to and the epidemiology, identification, and management of donor-derived infectious disease transmission shall be reviewed.