Hybrid electric vehicles have demonstrated their ability to significantly reduce fuel consumption for several medium- and heavy-duty applications. In this paper we analyze the impact on fuel economy of the hybridization of a tractor-trailer. The study is done in PSAT (Powertrain System Analysis Toolkit), which is a modeling and simulation toolkit for light- and heavy-duty vehicles developed by Argonne National Laboratory. Two hybrid configurations are taken into account, each one of them associated with a level of hybridization. The mild-hybrid truck is based on a parallel configuration with the electric machine in a starter-alternator position; this allows start/stop engine operations, a mild level of torque assist, and a limited amount of regenerative braking. The full-hybrid truck is based on a series-parallel configuration with two electric machines: one in a starter-alternator position and another one between the clutch and the gearbox. The truck can run in electric propulsion mode at low speed/low power, the engine being either shut down or running in series mode. That increases the braking energy recuperation rates. We first analyze the benefits of the two hybrid configurations on standard cycles. We then compare fuel economy results from a short standard highway cycle with a longer cruising scenario to illustrate the sensitivity of the benefits to the drive cycle. Finally, using simulation involving a grade scenario of periodical hills that we designed for this project, we show hybridization can be beneficial on hilly terrain.