Antibodies play a key role in the immune response. Since antibodies bind antigens with high specificity and tight affinity, Monoclonal antibodies are therapeutic drugs and used for vaccine development. Antibody engineering, biophysical characterization, and structural data have provided a deeper understanding of how antibodies function, and how to make better drugs. Isothermal titration calorimetry (ITC) is a label-free binding assay, which measures affinity, stoichiometry, and binding thermodynamics for biomolecular interactions. This review article describes ITC, and discusses several applications on how data from ITC provides insights into how antibodies function, guide antibody engineering, and aid design of new therapeutic drugs.