1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) rose through the ranks of organic solvents because of its unique set of physicochemical properties, becoming a solvent of choice in dominant areas of homogeneous catalysis, including acid catalysis, transition metal catalysis, photocatalysis, and organocatalysis. Its use not only allows re-imagining of well-established transformations but also unlocks eluding ones, representing new opportunities for future synthetic development.