With the increasing reliance on tissue allografts in orthopedic reconstructive and sports surgery, there is a realistic concern on behalf of both the surgeon and the patient as to the safety of these implanted tissues and the possibility of disease transmission. New Food and Drug Administration guidelines in association with independent agency scrutiny have served to decrease this risk in light of recent publicized reports of infection transmission associated with allograft use. In addition, tissue banks are constantly developing new proprietary techniques for allograft processing and sterilization. However, clinical studies are needed to validate disinfection efficacy and to evaluate the effect of these processes on tissue structural properties. This article serves as a review of historical disease transmission, current governmental and nongovernmental tissue regulations, and specific processing techniques used by tissue banks.