The global fleet of powered two-wheelers (PTWs) is constantly increasing. In many countries, motorcycles, scooters and mopeds play a significant role in mobility, particularly in many of the world’s large cities. As such, PTWs are becoming an important component of the transport system. However, they represent an important challenge for road safety. PTW riders are at far more risk than car drivers per kilometre ridden in terms of fatalities and severe injuries entailing long-term disability. Moreover, they have not benefited from safety improvements at the same pace as car occupants over recent decades. Addressing the issue of PTW safety is thus an essential contribution to the success of the United Nations’ Decade of Action for Road Safety, which aims at halving the expected number of road deaths worldwide by 2020. This report reviews recent trends in powered two-wheeler crashes, the factors contributing to these crashes and their severity. It describes a set of countermeasures targeting user behaviours, the use of protective equipment, the vehicles and the infrastructure. Finally, it discusses motorcycle safety strategies in the context of a safe system.