This paper compiles, evaluates and analyses information from different data sources on accidents and health, road transport and economic performance in a comprehensive manner to assess the size and impact of road accidents and injuries in regions under increasing motorization. Strategies based on global road safety improvement experiences are presented. In addition the paper aims at discussing a way forward by indicating opportunities and countermeasures that could be implemented to achieve a new level of safety in these regions. The data used comes from e.g. World Health Organization (WHO) and World Bank. Estimations on costs due to road transport injuries are presented. The results clearly demonstrate that road safety is causing large problems and costs with an enormous impact on the well-being of people, economy and productivity. For example, according to our analysis, the loss to the economy in Latin America is more than 130 billion US$ or 2.8 % of GDP. In many of low and middle-income countries the yearly number of fatalities and injuries is still increasing. Vulnerable road users (pedestrians, cyclists and motor cyclists) are particularly at risk. Reliable accident data are imperative to determine evidence based intervention strategies and monitor the success of these interventions and analyses. When comparing data it is clear that there are large problems in official statistics in several countries. The lack of good high quality accident data should, however, not be an excuse to postpone measures. Future trends in road transport and lessons learned from best practices in high-income countries are reviewed. The paper also proposes measures beyond the Decade of Action Plan for Road Safety 2011-2020, with respect to vulnerable road users, infrastructure, vehicle technology and truck and bus safety and discusses the implications for road safety in the UN’s new Sustainable Development Goals.