Abstract Calorimetry belongs to the most important experimental techniques. It is the only experimental method allowing for direct measurements of various physical and chemical processes and reactions. When appropriate model is used, analysis of results on molecular level is possible. This paper is devoted to use of solution calorimetry for investigation of two and three component liquid systems. Special attention is paid on results of dissolution enthalpy and heat capacity measurements. Several ways for analysis of the obtained results are presented. The course of standard enthalpies of solution versus mixed solvent composition can serve as a principal basis of the physico-chemical characteristics of investigated solutions. A quantitative measure of energetic effect of solute–solute interactions in solution can be obtained from analysis of the so-called enthalpic pair interaction coefficients derived from McMillan–Mayer theory. The Mastroianni, Pikal and Lindenbaum “cage model” and model of selective solvation proposed by Covington are useful in discussion of the dissolution enthalpies of hydrophobic solutes in water–organic cosolvent mixtures. Finally, the application of two-point scaling approach to the description of heat capacity function in microheterogenic systems is presented and discussed.