A key strategy to improving the real-world fuel consumption and emissions of medium and heavy duty vehicles is the hybridization and alternative fueling of these applications. Unlike the passenger vehicle market, medium and heavy duty applications are typically comprised of a range of components from a variety of manufacturers. The current diversity and size of the market, as well as their applications demands considerable thought with regards to fuel efficiency and emission compliance. Medium and heavy duty applications have the ability to be successfully hybridized and fueled in ways that are not currently, or would not be practical within a passenger vehicle. This drives increased vertical integration of the propulsion and accessory components. However, medium and heavy duty manufacturers have been prevented from certifying a full vehicle level platform due to the current engine certification requirements. This lack of a vehicle level certification procedure limits the ability to optimally integrate conventional and hybrid platforms and limits the applicability of certification results to real-world improvements in fuel economy and emissions. To determine future opportunities and direction, a joint study was initially conducted by Navistar and ANL  and then later followed-up by Navistar internally to address how such technologies may be practically integrated into medium and heavy duty applications. This study included the evaluation of real world vehicle data, current certification, regulatory processes and marketing data. Many challenges and opportunities were discovered. This paper follows up on the challenges and opportunities in the adoption of these technologies within medium and heavy duty applications with respect to current market characteristics, past and current lessons from within the passenger vehicle market, regulatory barriers in the medium and heavy duty market, the diversity of options and their challenges, as well as proposed opportunities for widespread adoption.