In November 2007, a liver transplant recipient was confirmed to have human immunodeficiency virus (HIV) and hepatitis C (HCV) infection after the organ procurement agency notified our institution that the donor has been HIV and HCV positive. We reviewed medical records and the collected blood sample results for HIV and HCV testing. A 66 year old female with nonalcoholic steatohepatitis cirrhosis underwent liver transplantation. The donor was a male who had sex with men who received multiple blood transfusions during resuscitation. Preoperative testing for HIV and HCV antibodies were negative for both donor and recipient. Ten months later, HIV and HCV were identified with nucleic acid testing in the recipient and in the stored donor sera. This is the first reported case of HIV transmission from solid organ transplantation in 20 years, and the first ever reported case of simultaneously transmitted HIV and HCV. The current case represents a high risk donor with newly-acquired HIV and HCV who transmitted the diseases during the window period of the infections. In this era of organ shortages one option would be avoidance of any high-risk donor organs. Another option would be to continue the use of such organs with appropriate informed consent, acknowledging the limitations of current screening tests for HIV and HCV. This report should serve as a wake-up call to the transplant community to consider revamping organ donor screening for HIV and HCV using nucleic acid testing as well as reconsidering the ongoing use of high-risk donors. Liver Transpl 14:1603–1608, 2008. © 2008 AASLD.