Hydrothermal liquefaction (HTL) is a promising technology for converting wet plant biomass directly to liquid fuels and chemicals. However, some aspects of the technology are not fully understood and still disputed. The reactor material constraints and difficulties coupled with the formation of unwanted products are the main challenges limiting the applications of the technology. In addition, heat and mass transfer limitations in the reaction system result in a lower conversion efficiency and selectivity, of which the later would make it difficult and expensive for products separation, purification, and/or modification of the products. This paper discusses the challenges and current status of possible solutions to the challenges, focusing on the need of developing a special plug-flow reactor for scaling up of the HTL process. (C) 2016 Elsevier Ltd. All rights reserved.