Advanced technology heavy-duty vehicles such as hybrids present unique regulatory challenges. Hybrids employ an additional energy source in conjunction with an internal combustion engine for motive power, and the interactions between the engine and the hybrid components affect criteria pollutant emissions and fuel consumption. Often, an engine installed in a hybrid vehicle will operate very differently from the same engine installed in a conventional vehicle driven over the same route. One of the difficulties in integrating vehicles such as hybrids into regulatory programs is developing the proper certification test procedures for criteria pollutant and greenhouse gas (GHG) emissions so that these advanced technologies and vehicles are evaluated fairly and consistently as compared to their conventional counterparts. This paper seeks to inform policy makers of the alternatives for moving toward more holistic approaches to testing and certifying powertrain systems and complete vehicles. The first part of the paper describes and compares the options for testing the emissions and fuel efficiency performance of heavy-duty vehicles from a technical perspective. The paper then goes on to discuss some of the specific regulatory challenges posed by the fact there are a myriad of test method and test cycle options and combinations that could potentially be used in a certification program. Finally, the paper concludes with an examination of the opportunities and challenges of developing a “world harmonized” certification procedure for heavy-duty hybrid and advanced technology vehicles.