HCV infection poses a significant health problem, with millions of individuals infected worldwide. Furthermore, a common means of infection is injection drug use. Although some treatments exist, a substantial portion of the patient population remains resistant to current HCV therapies. Clearly, new and novel therapeutics are needed. RNAi is a cellular regulatory mechanism whose use has revolutionized molecular biology. One of the most exciting potentials of RNAi involves using it to design anti-HCV therapies. This meeting will discuss recent progress in using RNAi tools to attack in vitro and in vivo models of HCV infection and the potential of RNAi as an antiviral therapeutic in humans. RNAi functions by targeting specific messenger RNAs (mRNAs). Recently, researchers have demonstrated that small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) can be used to target HCV mRNAs in vitro and are working to develop nonhuman animal models to refine these therapies in vivo. This work poses many challenges; this meeting plans to address the following four hurdles involved in developing RNAi treatments: (1) in vivo siRNA and shRNA delivery, (2) the efficacy of RNAi action, (3) the specificity and adaptability of targeting, and (4) defining any unique characteristics of HCV-infected drug users. A number of prominent RNAi and HCV researchers will discuss the problems currently facing the field and the potential for translating this work into clinical applications.