This manuscript describes the research and development undertaken at Pacific Northwest National Laboratory subsequent to an earlier bio-oil hydrotreating historical development review in 2007. It also includes the implications for future development needs related to hydroprocessing of biomass fast pyrolysis bio-oil for liquid hydrocarbon fuels production. The results of the research, the needs and implications for additional research and development, as well as the future potential for technology transfer to industrial application are included. The progress over the 10 years of research can be captured by the technoeconomic assessment in the reduction in cost of the product by nearly 80% of the starting assessment. Design catalyst lifetime was extended from< 10 days to half a year through improvements in operational details such as catalyst formulations and operating temperatures, with introduction of sulfur guard beds (with regeneration protocols) to protect precious metal catalyst in the low-temperature stabilization bed, as well as the recycle of the heavy ends of the hydrotreated product back to the hydrotreater for product finishing. Attempted operation of an ebullated bed reactor system was unsuccessful but enlightening as to the complex phase structure experienced in bio-oil hydrotreating.