Pyrolytic biofuels have technical advantages over conventional biological conversion processes since the entire plant can be used as the feedstock (rather than only simple sugars) and the conversion process occurs in only a few seconds (rather than hours or days). Despite decades of study, the fundamental science of biomass pyrolysis is still lacking and detailed models capable of describing the chemistry and transport in real-world reactors is unavailable. Developing these descriptions is a challenge because of the complexity of feedstocks and the multiphase nature of the conversion process. Here, we identify ten fundamental research challenges that, if overcome, would facilitate commercialization of pyrolytic biofuels. In particular, developing fundamental descriptions for condensed-phase pyrolysis chemistry (i.e., elementary reaction mechanisms) are needed since they would allow for accurate process optimization as well as feedstock flexibility, both of which are critical to any modern high-throughput process. Despite the benefits to pyrolysis commercialization, detailed chemical mechanisms are not available today, even for major products such as levoglucosan and hydroxymethylfurfural (HMF). Additionally, accurate estimates for heat and mass transfer parameters (e.g., thermal conductivity, diffusivity) are lacking despite the fact that biomass conversion in commercial pyrolysis reactors is controlled by transport. Finally, we examine methods for improving pyrolysis particle models, which connect fundamental chemical and transport descriptions to real-world pyrolysis reactors. Each of the ten challenges is presented with a brief review of relevant literature followed by future directions which can ultimately lead to technological breakthroughs that would facilitate commercialization of pyrolytic biofuels.