Partition coefficients for varied compounds were determined for the organic solvent–formamide biphasic partition system where the organic solvent is 1,2-dichloroethane, 1-octanol or isopentyl ether. These partition coefficient databases are analyzed using the solvation parameter model facilitating a quantitative comparison of the formamide-based partition systems with other totally organic and water-based partition systems. Formamide is shown to be a less cohesive and hydrogen-bond acidic solvent than water with similar hydrogen-bond basicity and dipolarity/polarizability. Compared with other organic solvents its higher cohesion, dipolarity/polarizability and hydrogen-bonding capability make it a useful base solvent for forming biphasic partition systems with a range of system properties obtained through variation of the counter solvent. Formamide–organic solvent systems offer a complementary approach to water-based partition systems for sample preparation and the determination of descriptors for compounds virtually insoluble in water or unstable in water.