Recent developments in supercritical fluid chromatography (SFC) have highlighted the applicability of this technique for the analysis of highly polar compounds. The combination of polar stationary phases and CO2-based mobile phases with an increasing presence of liquid co-solvent (up to 100%) has enabled to further expand the application field of SFC towards a variety of samples such as polar endogenous metabolites, plant extracts, water-soluble vitamins, pesticides, sugars, peptides and so on. In this evolution, a key role was played by the addition of up to 5e10% of water in the liquid co-solvent. Moreover, the presence of water enabled higher concentrations of additives, up to 75e100 mM in some cases. These improved conditions were fundamental in expanding the applicability range of SFC. Overall, SFC has demonstrated its evolution into a mature technique capable of offering a true alternative to liquid chromatography for the analysis of polar compounds.