A major importance of macromolecular crowding to biological systems stems from its effect on protein folding. The underlying physical mechanism by which macromolecular crowding helps to stabilize proteins in their folded state is often explained in terms of excluded volume - the volume inaccessible to the proteins due to their interaction with macromolecular crowders. This notion goes back to Asakura and Oosawa, who have described depletion forces induced by steric, hard-core, interactions. A hallmark of the mechanism inferred from the above is that the effect is completely a-thermal, and thus completely entropic. These ideas were also proposed to explain why small cosolutes, namely protective osmolytes, which are preferentially excluded from proteins, also shift the protein folding equilibrium towards the folded state. However, it has been shown by various methods, both experimental and theoretical, that depletion forces are not always entropic in nature.