Mitigating CO2 emissions from long-haul commercial trucking is a major challenge that must be addressed to achieve substantial reductions in greenhouse gas (GHG) emissions from the transportation sector. Extensive recent research and development programs have shown how significant near-term reductions in GHGs from commercial vehicles can be achieved by combining technological advances. This paper reviews progress in technology for engine efficiency improvements, vehicle resistance and drag reductions, and the introduction of hybrid electric powertrains in long-haul trucks. The results of vehicle demonstration projects by major vehicle manufacturers have shown peak brake thermal efficiency of 55% in heavy-duty diesel engines and have demonstrated freight efficiency improvements of 150% relative to a 2009 baseline in North America. These improvements have been achieved by combining multiple incremental improvements in both engine and vehicle technologies. Powertrain electrification through hybridization has been shown to offer some potential reductions in fuel consumption. These potential benefits depend on the vehicle use, the details of the powertrain design, and the duty cycle. To date, most papers have focused on standard drive cycles, leaving a research gap in how hybrid electric powertrains would be designed to minimize fuel consumption over real-world drive cycles, which are essential for a reliable powertrain design. The results of this paper suggest that there is no “one-size-fits-all” solution to reduce the GHGs in long-haul trucking, and a combination of technologies is required to provide an optimum solution for each application.