Vaccine-preventable disease levels in the United States are at or near record lows. Most parents today have never seen a case of diphtheria, measles, or other once commonly encountered infectious diseases now preventable by vaccine administration. As a result, some parents wonder why their children must receive shots for diseases that do not seem to exist. Myths and misinformation about vaccine safety abound and can confuse parents who are trying to make sound decisions about their children's health care. However, we cannot take continued high immunization coverage levels for granted. A successful vaccination program, like a successful society, depends on the cooperation of every individual to ensure the good of all. This review outlines for clinical allergists-immunologists the molecular basis for the risks and adverse events associated with vaccine administration so that they can be better informed as experts on vaccine-associated adverse reactions.