Interruption of transmission has always been one of the most attractive approaches for infection control. The technologies available were severely limited before the development of appropriate vaccines. Mathematically, the proportion of those who need to be immune to interrupt transmission can be derived from the Ro, which represents the number of new cases infected by a single case when all contacts are susceptible. Purely respiratory infections have critical characteristics affecting transmission that are different from key childhood vaccine-preventable diseases spread by the respiratory route. They include frequent reinfections and antigenic changes of the agents. Pragmatic approaches to understanding their potential effect can be found in experimental and programmatic use of vaccines such as those for Haemophilus influenzae type b and influenza virus infections. Results of these experiences can in turn strengthen the development of transmission theory.