Organ transplantation, including of the heart, lung, kidney, liver, pancreas, and small bowel, is considered the therapy of choice for end-stage organ failure. Each year, over 70,000 organs are implanted worldwide. One donor may provide multiple organs, as well as corneas and other tissues, for multiple recipients. The degree of risk for transmission of infection carried with grafts, notably of viruses, is largely unknown and, for a specific organ, difficult to assess. The approach to microbiological screening of organ donors varies with national and regional regulations and with the availability and performance of microbiological assays used for potential donors. Transmission of both expected or common, and unexpected infections has been observed in organ transplants, generally recognized after development of clusters of infections among recipients of organs from a common donor. Other than for unusual or catastrophic events, few data exist that define the incidence and manifestations of donor-derived infections or the ideal assays to use in screening to prevent such transmissions. Absolute prevention of the transmission of donor-derived infections in organ transplantation is not possible. However, improvements in screening technologies will enhance the safety of transplantation in the future.