There remains a great need to develop vaccines against many of the pathogens that infect mucosal tissues or have a mucosal port of entry. Parenteral vaccination may protect in some instances, but usually a mucosal vaccination route is necessary. Mucosal vaccines also have logistic advantages over injectable vaccines by being easier to administer, having less risk of transmitting infections and potentially being easier to manufacture. Still, however, only relatively few vaccines for human use are available: oral vaccines against cholera, typhoid, polio, and rotavirus, and a nasal vaccine against influenza. For polio, typhoid and influenza, in which the pathogens reach the blood stream, there is also an injectable vaccine alternative. A problem with available oral live vaccines is their reduced immunogenicity when used in developing countries; for instance, the efficacy of rotavirus vaccines correlates closely with the national per capita income. Research is needed to define the impact of factors such as malnutrition, aberrant intestinal microflora, concomitant infections, and preexisting immunity as well as of host genetic factors on the immunogenicity of these vaccines.