Vectors based on RNA viruses have played an important role in modern vaccine development. Different types of RNA viruses including retroviruses, lentiviruses, alphaviruses, flaviviruses, rhabdoviruses, measles viruses, paramyxoviruses, reoviruses, and picornaviruses have been applied for immunization against infectious diseases and cancer. Viral pathogens such as influenza virus, human immunodeficiency virus, Ebola virus, Zika virus, and SARS-CoV-2 have been targeted, showing robust immune responses and protection against challenges with lethal doses of viruses in preclinical animal models. Moreover, clinical trials have demonstrated protection against challenges with Ebola virus in humans leading to vaccine approval by the FDA and the EMA. Similarly, RNA virus-based cancer vaccines have been developed, also showing therapeutic efficacy in preclinical studies and clinical trials. Particularly, self-amplifying RNA viruses have garnered attention for further vaccine development and can be utilized as recombinant virus particles, RNA replicons, and layered DNA plasmids. RNA virus-based vaccine development against COVID-19 has demonstrated efficacy in preclinical studies and currently clinical evaluation is in progress.