This paper is a review of the thermodynamics of retention in hydrophobic interaction chromatography (HIC) with mildly hydrophobic stationary phases and aqueous salt solutions usually employed in protein purification. Since the role of salt in HIC has been well documented, our focus was to investigate the temperature effect on the retention behavior in HIC and to compare the results with those obtained for other processes driven by the hydrophobic effect. Using nonpolar dansyl amino acids as model compounds, retention data obtained on three stationary phases yielded nonlinear van’t Hoff plots in the temperature range from 5 to 50 degrees C. Thermodynamic analysis of the data revealed significant heat capacity effects. The enthalpy and entropy changes were large and positive at low temperatures, decreased with increasing temperature, and became negative at high temperatures. The results parallel those of calorimetric studies on other processes based on the hydrophobic effect, such as dissolution in water of nonpolar liquids, gases, and solids as well as protein folding. Thermodynamic parameters from HIC measurements also confirmed the existence of certain exothermodynamic relationships, such as enthalpy-entropy compensation and molecular area correlations. In order to examine at the molecular level the energetics of HIC retention as well as the dissolution of nonpolar gases in water, the pertinent thermodynamic parameters were expressed in terms of nonpolar molecular area and interfacial tensions by employing the solvophobic theory. It was found that these expressions from HIC and dissolution data are nearly identical, thus confirming the mechanistic identity of the two processes.