Recent changes in testing technologies for syphilis and HIV present diagnostic laboratories new opportunities and challenges. Matthew Golden, division of allergy and infectious disease at the University of Washington, discusses newly available enzyme immunoassays for syphilis and new approaches to testing for HIV, including rapid point-of-care tests and pooled HIV RNA testing. Golden emphasizes how laboratories can help clinicians interpret test results and choose the most appropriate test for their environment. From the Series:Laboratory Medicine Grand Rounds