Immunisations have been one of the most cost-effective public health interventions in human history. Despite remarkable progress, several challenges face immunisation programs worldwide. Paradoxically, despite vaccines' clear effectiveness in reducing risks of diseases that were previously widely prevalent and caused substantial morbidity and mortality, current vaccination policies have become increasingly controversial due to concerns about vaccine safety. Vaccines, like other pharmaceutical products, are not entirely risk-free. While most known adverse effects are minor and self-limited, some vaccines have been associated with very rare but serious adverse effects. Because such rare effects are often not evident until vaccines come into widespread use, ongoing surveillance programs to monitor vaccine safety are needed. Such monitoring will be essential if the public is to accept the increasing number of new vaccines made possible by biotechnology. The interpretation of data from vaccine safety research is complex and is associated with some uncertainty. Effectively communicating this uncertainty and continuing to improve understanding of rare risks and risk factors are essential for "mature" immunisation programs to maintain public confidence in immunisations.