Treatment with tumor necrosis factor-alfa inhibitors and other systemic medications increases the risk of reactivating a latent tuberculosis (TB) infection. Therefore, screening for latent TB infection is important in dermatology patients eligible for treatment with these medications. Although the tuberculin skin test (TST) has its limitations, it has been the standard choice for diagnosis of latent TB infection. Since the development of interferon gamma release assays (IGRAs), the role of the TST has been re-evaluated and IGRAs have increasingly been incorporated into national guidelines. Although there are situations when either test may be performed, in individuals who have received a BCG vaccination and in those who are unlikely to return for a TST reading, IGRAs may be particularly helpful in distinguishing patients at risk for TB. This article discusses the advantages and disadvantages of both the TST and the IGRA and presents a summary of the Centers for Disease Control and Prevention 2010 guidelines for using IGRAs.