In Europe, the first publications addressing the impacts of roads on wildlife date back to the 1930s. In the 1960s, the first measures were taken to prevent such impacts. In the following decades, road mitigation measures have been applied across most parts of Europe. In the 1990s, the Infrastructure and Ecology Network Europe was established, a network of experts that aims to develop and exchange knowledge and best practices to promote safe and ecologically sustainable transport infrastructure. In 2003, the network developed the Wildlife and Traffic Handbook, the first European manual with practical guidelines for preventing, mitigating, or compensating impacts of transportation infrastructure. Here, we synthesized the current state of knowledge on road impacts and mitigation in Europe and identified a set of research needs. The most prominent impact may be road mortality, with estimates of millions of animals killed on roads every year. Since the European continent has one of the highest road densities in the world, road-related habitat loss, degradation, and fragmentation seem to be significant long-term threats to European wildlife populations. Research on the effectiveness of some measures showed that wildlife crossing structures may help animals safely cross roads, and fences are appropriate to prevent roadkill if designed, installed, and maintained properly. The European road network will be extended through the initiative of the European Commission to develop a Trans-European Transport Network (TEN-T). Simultaneously, there is the aim to develop a coherent and resilient TEN-N of protected areas. In this respect, careful designing of all nodes where the European road network and ecological network meet is essential.