Publisher Summary The limits of existence of life have been pushed to unexpected extremes of pressure, temperature, pH, salinity, etc., for the last several decades. Hydrostatic pressure significantly influences the structural properties and thus the functional characteristics of cells. However, these have not prevented the invasion of cold and high pressure habitats of deep-sea organisms. The effect of high pressure on bimolecular systems can yield a wealth of enlightening new information on their structure, energetic phase behavior and on their transition kinetics, and might promise fulfillment of the challenge set forth by W. Kauzmann when discussing the thermodynamics of unfolding of proteins. Further, pressure may also serve as valuable thermodynamic tweezers to study protein–protein interaction and aggregation. Ambitious goals that are based on the rational modification of molecular structures functions with relationships by pressure. The chapter demonstrates that pressure dependant studies can help delineate the free energy landscape of proteins and hence help elucidate which features are essential in determining the uniqueness and stability of the native conformational style. References are also given in the chapter.