Other than in Japan, medium and heavy duty vehicles (MHDVs) are not regulated despite accounting for a significant portion of the fuel consumed (about 26% in the US in 2008). Government agencies worldwide are currently evaluating options to address that issue. Due to the large number of vehicle applications, some of them being "one of a kind", vehicle modeling and simulation offers an attractive solution to medium and heavy duty regulations. This paper discusses the advantages and challenges of vehicle simulation to support regulations.