A few pitfalls associated with the Anfinsen's thermodynamic hypothesis are discussed. The most profound one is the misinterpretation of the Anfinsen 'thermodynamic hypothesis' in terms of the Second Law of Thermodynamics. This misinterpretation has inspired many scientists to search for a global-minimum in the Gibbs energy as a function of the conformation of the protein, sometimes referred to as the Gibbs energy landscape. Such a minimum in the Gibbs energy is different from the minimum required by the Second Law of Thermodynamics. (C) 2011 Elsevier B.V. All rights reserved.