Hepatitis C causes a chronic infection causing progressive liver damage and cancer, and is transmitted via contaminated blood. Despite the availability of direct acting antivirals that cure hepatitis C infection in >98% of treatments, 1.5 million new infections occur each year, and 58 million people globally live with hepatitis C, including almost 4 million adolescents. To achieve elimination of hepatitis C, a vaccine to prevent infection is required. A vaccine for hepatitis C must provide broad cellular and humoral immunity effective against the 8 genotypes (30% difference at nucleotide level) and at least 86 subtypes (20% difference at nucleotide level) and represents a major challenge. To address this challenge, we have explored the use of recombinant protein, virus like particles, viral vectored vaccines and mRNA to deliver HCV sequences to generate immune responses in small animal studies. Our results suggest that E1E2 uses multiple immune evasion mechanisms to minimise the production of neutralizing antibodies, instead enhancing the production of type-specific and non-neutralizing antibodies. Protein engineering is required to focus and enhance the immune response on broadly neutralizing antibody epitopes. For cellular immunity, delivery of multiple conserved epitopes across the HCV sequence results in the generation of polyspecific and polyfunctional CD4+ and CD8+ T cell responses. Combining B and T cell immunogens into a single vaccine generates broadly reactive neutralizing antibodies and T cell immunity, however, alters antibody specificity. While the development of a vaccine to prevent HCV is theoretically possible, experimentally testing efficacy in humans may be the biggest hurdle to overcome, and likely only be possible using a human challenge model.