Because hepatitis C virus is etiologically involved in about half the cases of the world's most common cancer, hepatocellular carcinoma, and because this virus is likely to continue to spread in most of the developing world for many years, the authors believe that development of a prophylactic vaccine is imperative. Numerous approaches are available to overcome the many impediments which make the development of an HCV vaccine difficult. Such impediments include the many viral genotypes and quasispecies of HCV and the association of virions with host lipids. It is likely that overcoming these impediments will require a vaccine which induces a strong cell-mediated response. The most promising approach seems to be DNA-based immunization or a prime-boost regimen with DNA priming and boosting with a viral vector. Potentiation of responses with adjuvant strategies will probably be necessary. Hepatitis C virus immunization is in an early stage of development. Given the explosive growth in the understanding of immunology, progress should be rapid.