Solubilization of drugs in aqueous phases of liquid and semisolid environment is typically achieved by co-solvents or surfactants. On contrast, solubilization by means of hydrotropic agents, i.e., small hydrophilic organic compounds like urea or citric acid, is little explored in the context of pharmaceutical formulations. Especially, with regard to topical dosage forms, however, hydrotropic solubilization can provide valuable alternatives to establish solubilization approaches. A difficulty of employing hydrotropic solubilization was that its extent could not be predicted for different drug molecules. Using a chemically heterogeneous set of 12 compounds relevant for dermatology (with overall 16 different logD values tested), we were able to demonstrate that hydrotropic effects of urea can be predicted by logD values of drugs. All compounds with logD values between 2 and 4.5 showed a solubility enhancement factor (EF) of >5 in 40% aqueous solutions of urea. For logD values below 2 or above 5, only EF < 5 were found. For some compounds, e.g., diclofenac (pH 4) and prednicarbate could achieved only EF > 5 at 5% urea and EF > 250 at 20% urea.