The supply of conventional light petroleum is being depleted, leading to increasing dependence on unconventional oil sources such as heavy oil. Heavy oil often contains a significant amount of heavy fraction asphaltene. During heavy oil upgrading, asphaltenes promote the formation of high-molecular-weight coke, which can cause issues, including catalyst deactivation, reduced heat transfer efficiency, and pipeline blockage. Hydroprocessing, in which hydrogen is reacted with heavy oil fractions at medium-to-high temperatures, selectively removes impurities and can achieve a much higher liquid oil yield than other processes. However, asphaltenes can interfere with hydroprocessing, limiting its conversion efficiency. Thus, proper asphaltene treatment is essential to developing effective hydroprocessing processes and catalysts. The effects of hydroprocessing operating conditions on asphaltenes have been extensively studied in recent decades. In light of that, this review summarizes the state of the art of the research in this field. More specifically, the effect of different operation parameters on asphaltene molecules' chemistry and physical behavior during hydroprocessing is discussed. Furthermore, methods to mitigate fouling and achieve a deep conversion of both heavy oil components and asphaltene are suggested. © 2020 Elsevier B.V.