© Springer International Publishing Switzerland 2014. All rights reserved. Nasal delivery of vaccines occurred over a millennium ago in China, where ground scabs from small pox lesions, presumably containing live virus, were sniffed. This practice was the basis for early vaccination with live virus in Europe in the eighteenth century. In the past decade, a number of reports have focused on new antigens, adjuvants, and delivery systems, but few approaches have entered development as a clinical candidate. This chapter outlines the critical steps needed to create a comprehensive integrated strategy adopting an antigen, with candidate physical and biochemical adjuvants, in a delivery system. There is a need to define unique formulation and device performance properties, evaluate dose sparing achieved through novel construction and adjuvancy, and develop rapid screening methods to identify toxic formulations.