Vaccination is one of the most cost-effective public health interventions. However, the EU is facing increasing outbreaks of vaccine preventable diseases, with some fatal cases of measles. This paper reviews the main factors influencing vaccination uptake, and assesses measures expected to improve vaccination coverage. Obstacles to vaccination include concerns about vaccine safety and side effects, lack of trust, social norms, exposure to rumours and myths, and access barriers. Responses fall into three broad categories. Regulation, including the introduction of mandatory vaccination, can be justified but it is important to be sure that it is an appropriate solution to the existing problem and does not risk unintended consequences. Facilitation involves ensuring that there is an effective vaccination programme, comprehensive in nature, and reducing the many barriers, in terms of cost, distance, and time, to achieving high levels of uptake, especially for marginalised or vulnerable populations. Information is crucial, but whether in the form of public information campaigns or interactions between health workers and target populations, must be designed very carefully to avoid the risk of backfire. There is no universal solution to achieving high levels of vaccine uptake but rather a range or combinations of options. The choice of which to adopt in each country will depend on a detailed understanding of the problem, including which groups are most affected.