Needle exchange programs exist in every major population area in the United States and in many other countries. Some operate legally under emergency health decrees issued by local departments of health, with the stated intention of risk reduction through the removal of used injection equipment from use by injection drug users. It is theorized that this results in a reduced transmission of human immunodeficiency virus, hepatitis, and, possibly, other blood-borne diseases. Needle exchange programs also offer access to drug treatment programs for the participants. It is a difficult but necessary task to evaluate these programs. This article examines examples of evaluations attempted in the past and discusses the challenges of such evaluations. Experimental evaluations, economic program analysis, legal aspects, and risk-benefit assessment along with ethical aspects are considered. An outline of program evaluation is proposed. Needle exchange programs offer an opportunity to encourage risk reduction and to offer counseling and access to health care for individuals at high risk. It is essential that such programs demonstrate their effectiveness. Assumptions of efficacy are insufficient for health care in the twenty-first century.