Biomass fast pyrolysis is potentially one of the cheapest routes toward renewable liquid fuels. Its commercialization, however, poses a multi-scale challenge, which starts with the characterization of feedstock, products and reaction intermediates at molecular scales, and continues with understanding the complex reaction network taking place in different reactor configurations, and in the case of ... [Show full abstract] catalytic pyrolysis and upgrading on different catalysts. In addition, crude pyrolysis oil is not immediately usable in the current energy infrastructure, due to undesirable properties such as low energy content and corrosiveness as a result of its high oxygenate content. It, therefore, needs to be upgraded and fractionated to desired specifications. While various types of pyrolysis reactors and upgrading technologies are under development, knowledge transfer and closing the gap between theory and application requires model development. In-depth understanding of the reaction mechanisms and kinetics should be combined with the knowledge of multi-scale transport phenomena to enable design, optimization, and control of complex pyrolysis reactors. Finally, underpinning economic and environmental impacts of biofuel production requires expanding the system boundaries to include the overall process and supply chain. The present contribution aims at providing a comprehensive multi-scale review that discusses the state of the art of each of these aspects, as well as their multi-scale interactions. The study is mainly focused on fast pyrolysis, although reference to other types of pyrolysis technologies is made for the sake of comparison and knowledge transfer.