The review discusses the molecular origins of the forces and free energies that determine several things about proteins, and how experiment and theory reveal this information. The first subject is the stability of the folded, native structures. The second is the range of molecular mechanisms by which proteins find their way to those folded structures in laboratory environments. The third is the much more complex problem of how folding occurs in the cellular environment. This topic includes a discussion of crowding and of the roles of chaperone molecules. The review concludes with a discussion of protein aggregation and fibril formation and of misfolding and therapies associated with it.