The European Commission with the active contribution of NTUA, SWOV and KFV has published at the European Road Safety Observatory, the Main Factors causing Fatal Crashes Thematic Report, in which the role of key risk factors is quantified and discussed, based on the most recent international literature. These factors concern speeding, driving under the influence of alcohol, distraction and other psychoactive substances, and non-use of protective equipment. Addressing in priority the above causes of fatalities in Europe, through safe-by-design thinking, i.e. prevention, control and mitigation of the consequences of these errors, can contribute significantly towards the ambitious EU targets of halving fatalities by 2030 and eliminating them by 2050.