In recent years, sulfur regulations for transportation fuels have been considerably tightened. Moreover, there has been an increasing trend to refine heavier crudes, which are typically more difficult to process. Because of these reasons, it is becoming increasingly important to enhance the desulfurization efficiency of commercial heavy oil hydrotreating units. A molecular level understanding about the reactivity of sulfur compounds in heavy oils is expected to assist the optimization of the heavy oil hydrotreaters. Unfortunately, the desulfurization chemistry in heavy oil range is enormously complex. As compared to the lower petroleum fractions such as gasoline/diesel, it is considerably more difficult to obtain a fundamental understanding about sulfur species in heavy oils. Studies dealing with fundamental aspects of heavy oil desulfurization have been addressed in this minireview. The following related topics have been reviewed: (a) characterization of sulfur compounds, (b) kinetics/reactivity of individual sulfur molecular groups, (c) mechanisms/pathways for desulfurization, and (d) model compound studies.