Atomic-level structural information and advances in synthetic biology and nanotechnology have created new opportunities for generating vaccines in a way that has not been possible using traditional methods. These novel approaches to recombinant vaccine design are opening doors to the development of vaccines against challenging targets. In this chapter, we discuss the exceptional humoral immunogenicity of virus-like particles (VLPs) and related nanoparticles and their application to vaccine development. The emergence of this new category of vaccine platforms is based on recent insights from multiple fields of study, including immunology, virology, nanotechnology, structural biology, synthetic biology, and bioengineering. The multidisciplinary work on VLP and nanoparticle immunogens is already yielding dividends for public health, but is also likely to result in safer, more potent and broadly protective vaccines against a wide variety of human and animal pathogens, as well as target host proteins of interest.