Bio-oil has been identified as a major feedstock for the production of renewable fuels. As bio-oil has a high O-content, and therefore a low heating value and low stability over time, upgrading is desirable to remove the oxygen and to make it similar to crude oil. Here, we examine the two general catalytic routes for bio-oil upgrading: cracking and hydrodeoxygenation (HDO). Zeolite cracking is an alternative path in which acid zeolites are used as catalysts for the deoxygenation reaction. In these systems, hydrogen is not required, and so the operation is performed at atmospheric pressure. However, HDO is usually conducted under high H2 pressure in order to remove the O-containing compounds and hence to produce a high grade oil product. The catalysts employed for HDO are traditional hydrodesulfurization (HDS) catalysts, such as Co–MoS2/Al2O3, or metal catalysts. However, the life of the catalyst (more than 200 h on stream) has not been demonstrated. Of the two catalytic routes mentioned above, HDO appears to have the best potential, as zeolite cracking cannot produce fuels of an acceptable grade. Although HDO is considered the best option to produce transportation fuels of a grade and cost equivalent to present fossil fuels, several problems still have to be solved. An understanding of the carbon forming mechanisms and kinetics, an evaluation of the requirement for high pressure, and sustainable sources of hydrogen are some of the areas that have to be elucidated before the process can be commercialized.