Differential-scanning calorimetry is a thermodynamic technique widely used for studying drug-membrane interactions. This chapter provides practical examples on this topic, highlighting the caution to be taken in analyzing thermal data as well as scientific information that can be derived by the proper use of the technique. An example is given using model bilayers containing high concentration of the anesthetic steroid alphaxalone. It is shown that the breadth of the phase transitions and the maximum of the phase-transition temperature of the bilayer depend on the equilibration conditions before acquiring the thermal scan. In addition, the quality of the thermo-gram depends on its perturbation and incorporation effects; for dissecting these effects, a complementary technique such as solid-state nuclear magnetic resonance spectroscopy is necessary. Differential-scanning calorimetry is a useful technique to study the interdigitation effect of a drug by monitoring DeltaH changes. Cholesterol, a main constituent of membrane bilayers, appears to disrupt the interdigitating effect. In general, the thermal effects of the drug incorporated into a membrane bilayer depends on the drug stereoelectronic properties.