Vaccinology in the twenty-first century faces a highly complex situation given the remarkable evolutions which have recently occurred, creating a new era for immunisation policies in Europe. From a situation of vaccines targeted essentially against serious childhood diseases, we have moved to one of immunisation as a tool for preventing infectious diseases or their complications and outcomes in all age groups. At the same time, health technology assessment (HTA)—the evaluation of clinical effectiveness, cost-effectiveness and the larger impact of a health technology on patients and the health care system—has become crucial to the introduction of immunisation policies. This explains why the number of stakeholders involved in this process has grown. It now includes not only health authorities, their regulatory agencies and vaccine manufacturers, but also epidemiologists, economists, national and international advisory bodies and expert groups, scientific societies and even the general public through patient groups and/or politicians. They may have their own approaches, values and biases, but they all contribute to the implementation of immunisation policies from the long process of development all the way to registration and recommendations. With the new vaccines developed over the past decade, the number of vaccine-preventable diseases has risen from 22 to 25. But more importantly, new vaccines open new paradigms in the traditional concept of vaccinology. We are now dealing with new outcomes (prevention of disease/ medical or social consequences/impact on health care systems...) and new levels of investment owing to ever more refined biotechnologies and necessary investments in clinical development. The magnitude of recent changes requires a radical rethinking of vaccination policy-making at the country level as well as common approaches at the European Union (EU) level. Will the health care systems, and especially the EU, be able to cope with these challenges and ensure prompt accessibility of these innovative health measures to its citizens? One part of the answer inevitably entails revisiting the principles which have so far been the basis for the development and implementation of vaccination programmes. In order to begin answering the numerous questions arising as a result of the new era in vaccinology, two round tables devoted to vaccination were organised during the last two EUPHA (European Public Health Association) conferences (Montreux, Switzerland in 2006 and Helsinki in 2007). The first round table was meant to analyse the new paradigms inherent to current and future fields of vaccinology, whilst the second sought enhanced understanding of the decision-making process for introducing new vaccines in Europe. The presentations and discussions during the round tables gave rise to this special issue of the Journal of Public Health.