Tobacco mosaic virus (TMV) is an RNA virus that typically infects plants but has recently been adapted for vaccine development, owing to the suitability of the virions for modifications as nanoparticles. TMV also has a simple functional structure of a 6.4 Kb (+)-strand RNA encapsidated by a single coat protein, which permits facile genetic manipulation. In this review, we describe recent advances in the manipulation of TMV for the development of several different types of vaccines, including ones that induce antibody and T-cell responses that are protective in pathogen and tumor challenge animal models. Lastly, we describe how TMV self-assembly properties are being used to make a new mammalian RNA pseudovirus, that has unique characteristics for RNA and protein antigen delivery to antigen-presenting cells.