In September 2006, the US Centers for Disease Control and Prevention (CDC) released new guidelines calling for routine, voluntary human immunodeficiency virus (HIV) testing for all persons aged 13–64 years in health care settings. These guidelines were motivated, in part, by mounting evidence that the traditional approach of using risk factors to identify candidates for HIV testing is inadequate. Of the 1.0–1.2 million people in the United States thought to be infected with HIV, ~25% remain unaware of their infection, and nearly half of all infected patients develop acquired immunodeficiency syndrome ≤1 year after testing positive for HIV. Also contributing to the change in testing guidelines was recent evidence that routine HIV testing is cost-effective. Cost-effectiveness analysis, a method of assessing health care interventions in terms of the value they confer, reports results in terms of the resources that are required for the intervention to produce an additional unit of change in health effectiveness; more economically efficient programs are those with lower cost-effectiveness ratios. This article reviews the methods and results of cost-effectiveness studies in the United States and articulates why routine, voluntary HIV testing is not only of crucial public health importance but also economically justified.