Regulating the routing of trains carrying hazardous materials is considered. Possible regulatory approaches, insights from past accident experience, status of related research, estimating population exposure, and determining preferred routes are described. Some major conclusions are as follows:(a) Regulation can be accomplished by route designation or by setting routing standards, but speed reduction and time-of-day restrictions should also be considered;(b) Experience shows that only about one out of three accidents is track-related and that although routing to avoid such accidents would reduce their total number, the proportion of costly equipment-related accidents and high-severity derailments would increase in the absence of speed reduction or time-of-day restrictions;(c) Localized population exposure cannot be estimated with confidence using the leading national network models in their current form because of geographical inaccuracies and the high level of link aggregation;(d) Better data on track conditions and economic impacts are needed, along with better methods for preferred route determination that would consolidate the advances in risk assessment modeling with those in developing efficient routing algorithms.