More than one third of all road deaths in the Netherlands and more than two thirds of seriously injured casualties are cyclists. In recent years these shares have increased, despite the fact that the implementation of Safe System principles has been leading in road safety policy and has been successful in reducing the total number of road deaths. However, the annual number of fatalities among cyclists failed to decline and the number of injuries among cyclists has been increasing, especially in single-bicycle crashes. This raises the question why until now Safe System implementation has failed to contribute to the reduction of the number of casualties among cyclists. This question is urgent because of the goal to reduce the number of road deaths and serious traffic injuries in the Netherlands to (virtually) ZERO by 2050. This ambition is in line with the objectives of the European Union. The causes of the unfavourable developments in road safety for cyclists in the Netherlands and which problems require a solution are examined. This raises two questions: can improved implementation of Safe System measures reverse the negative trend, and can this result in ZERO cycling casualties in the future. The discussion involves investigating three dimensions: exposure, crash risk, and injury risk. The opportunities that technological developments may offer in future decades are also considered. It is concluded that Safe System implementation will include opportunities to make cycling considerably safer in the Netherlands. However, we face too many uncertainties to allow for developing scenarios that show how close the Netherlands will be to ZERO cyclists casualties.