Emtricitabine (FTC) is a new nucleoside agent that has activity against both human immunodeficiency virus (HIV) and hepatitis B virus. It is very similar to lamivudine (3TC) with respect to its activity, convenience, and safety and resistance profile. Indeed, with the exception of the longer intracellular half-life of triphosphate FTC, there is little to distinguish between the 2 drugs. Clinical trials comparing FTC with 3TC as part of a triple-drug regimen have demonstrated their equivalence, whereas a study comparing activity of FTC with that of stavudine demonstrated FTC's superiority. In clinical practice, the choice of 3TC versus FTC will most likely be made in the context of drugs coformulated with them. Although FTC is not formally approved for use in patients coinfected with HIV and hepatitis B virus, it is often a preferred choice for such patients when combined with tenofovir, which also has anti-hepatitis B virus activity. Recent treatment guidelines for the treatment of HIV infection by both the International AIDS Society-USA and US Department of Health and Human Services have placed FTC in combination with tenofovir, didanosine, or zidovudine in the preferred category of nucleoside backbone regimens for patients receiving antiretroviral therapy. © 2005 by the Infectious Diseases Society of America. All rights reserved.