The high-level heterologous gene expression provided by alphavirus vectors has accelerated their applications in vaccine development. The versatility of alphavirus vectors has allowed their use in the form of recombinant viral particles, naked RNA and layered DNA molecules for immunization. The most commonly used alphaviruses have been Semliki Forest virus, Sindbis virus and Venezuelan Equine Encephalitis virus. Numerous viral structural proteins have been used as antigens to generate neutralizing antibodies in immunized animals. Vaccination has demonstrated protection against challenges with lethal doses of viruses. Moreover, vaccination with tumor antigens has demonstrated prophylactic protection against cancer. Novel approaches include the application of RNA interference and microRNA. The other side of the coin is the development of vaccines against alphaviruses themselves, and typically the Chikungunya virus.