Differential scanning calorimetry (DSC) is a powerful and highly sensitive nonperturbing technique used for studying the thermodynamic properties of thermally induced transitions. The ability of DSC to measure the effect of ligand binding on phase transitions of lipid membranes makes this technique particularly suitable for understanding interactions between proteins and lipid membranes. This chapter provides the newcomer and experienced practitioner with a comprehensive overview of basic DSC theory and an understanding of the capabilities of DSC instrumentation. Emphasis is placed on detailed analysis of DSC data to assess the effects of proteins on biomimetic membranes.