The development of an enzyme-linked immunosorbent assay (ELISA) for screening blood for antibodies to HIV was a major milestone in the history of AIDS prevention and treatment. Since early 1985, the Centers for Disease Control and Prevention (CDC) has provided public funds to state and local health departments to support a national HIV counseling-and-testing (HIV CT) program directed toward persons at risk of transmitting or becoming infected with HIV. The implementation and ongoing development of this national program has often been marked by intense policy debate, especially in the area of mandatory testing. Furthermore, the lessons learned during its 11-year program history are highly relevant to understanding the challenges that might arise when implementing other new biomedical or behavioral HIV prevention technologies. Using the construct of public health infrastructure, this article describes key features, events, lessons learned, and future challenges of this evolving national prevention program.