Serologic testing for syphilis is a cornerstone of syphilis control efforts, but our objectives for doing it and the costs involved are not always recognized. Tests applied to individuals with symptoms or signs may be viewed as diagnostic tests, and tests applied to individuals with no clinical indications for testing may be viewed as screening tests. Infected individuals whom we detect through screening efforts are important, mostly from an individual and economic standpoint, because treatment will prevent the late complications of syphilis and thus avoid high medical costs. Because they are uncommonly infectious for others, however, they are relatively unimportant from a public health intervention standpoint. The prevalence of infection above which we should screen is based mostly on economic grounds, but is undetermined. We intuitively recognize such a threshold, however, when we use epidemiologic markers to restrict our efforts to groups in whom we think the yield is worth the effort (i.e., targeted [focused] screening). In deciding whether to institute or increase screening efforts for syphilis, we must consider not only the dollar costs of these efforts, but also the opportunity costs (i.e., what programs we will forgo so that we can devote our resources to the increased efforts). Similarly, because syphilis is not the only priority with which governments, health departments, and sexually transmitted disease programs must contend, any broader plan to significantly enhance syphilis control must acknowledge this reality and show the benefit, economic and otherwise, of its adoption.