Nanoparticles have the capacity to activate the immune system, based on both intrinsic particle characteristics and through the delivery of immune activating cargo. Co-delivery of antigens with adjuvants, such as cytokines, cytotoxic agents or pathogen-associated molecular patterns, presents opportunities for stimulating antigen-specific immune responses. This chapter highlights the immunogenic benefits of select chemotherapeutics and the use of nanoparticles to deliver immunogenic molecules and antigens. The influence of intrinsic nanoparticle properties and biological barriers on immune responses to nanoparticles is also discussed. In closing, a summary of nanoparticles approved for clinical use in the United States and examples of those approved in other countries are presented to highlight successes in nano-immunotherapy.