The first comprehensive studies on the structure and thermodynamics of membrane proteins have started revealing the exact architecture of these macromolecules and the physical-chemical rules behind their structures. In this review, the stabilities of several families of membrane proteins, obtained by using spectroscopic, calorimetric and single molecule techniques are surveyed. The data on the stability of membrane proteins are compared with those obtained in soluble proteins. The comparison indicates that although the number of particular atomic interactions is larger in membrane proteins than in soluble ones, the overall values are similar. The consensus is that some intrinsic properties of membrane proteins resemble those of soluble ones, but there are critical differences arising form the inter-molecular contacts with the surrounding membrane. Taken together, all these efforts improve our understanding of the universal forces governing protein folding, and will help in the design of membrane proteins in the near future.