This paper reviews the literature related to the complex chemical composition and multiphase nature of bio-oils and their practical implications. Over time, bio-oil forms separated phases due to purely physical phenomena (phase stability) or chemical composition changes in storage (aging reactions). Bio-oil multiphase behavior and the formation of separated phases are controlled by the complex chemical composition of these oils. Fast pyrolysis oils from woody biomass are typically observed in a single phase. However, feedstocks with high extractives content and/or high ash content commonly produce oils with more than one phase (an aqueous phase, an upper layer, and a decanted heavy oily phase). The first part of this Review focuses on the effects of feedstock composition, particle size, type of pyrolysis reactor, and condensation systems on bio-oil chemical composition and their impact on stable oils production. The second section reviews our current understanding of fresh bio-oil multiphase behavior and the effect of aging reactions. The use of phase diagrams as a tool to predict bio-oil phase stability is discussed. The third section focuses on bio-oil upgrading strategies based on the use of solvents and the production of emulsions. In this section we discuss the factors affecting phase equilibrium. This review highlights the importance of developing systematic studies to better understand bio-oil liquid-liquid phase equilibrium and the advantages of using phase diagrams. This understanding could have significant impact on the development of new bio-oil separation processes, on the development of new tools to produce stable bio-oils, as well as on the production of bio-oil-derived fuels. Understanding the complex nature of bio-oil multiphase behavior has been progressing over the years; however, more work is still needed to control these phenomena.