Diesel engines are preferred over spark ignition counterparts for heavy-duty applications and power generation plants because of their higher efficiency, durability, and productivity. Currently, the research interests have been propelled towards renewable and sustainable diesel fuels such as biodiesel in order to address the environmental and energy security challenges associated with these energy systems. However, the most challenging issue concerning large-scale production of biodiesel is its relatively high cost over fossil-based diesel owing to high feedstock and manufacturing costs. Therefore, cost-effective and eco-friendly biodiesel production technologies should be necessarily developed and continuously improved in order to make this biofuel more competitive vs. its petroleum counterpart. Accordingly, this paper comprehensively reviews biodiesel manufacturing techniques from natural oils and fats using conventional and advanced technologies with an in-depth state-of-the-art focus on the utmost important unit, i.e., transesterification reactor. The effects of the main influential parameters on the transesterification process are first discussed in detail in order to better understand the mechanisms behind each reactor technology. Different transesterification reactors; e.g., tubular/plug-flow reactors, rotating reactors, simultaneous reaction-separation reactors, cavitational reactors, and microwave reactors are then scrutinized from the scientific and practical viewpoints. Merits and limitations of each reactor technology for biodiesel production are highlighted to guide future R&D on this topic. At the end of the paper, the sustainability aspects of biodiesel production are comprehensively discussed by emphasizing on the biorefinery concept utilizing waste-oriented oils. (C) 2019 Elsevier Ltd. All rights reserved.