Assessing the actual role of entropic forces in controlling both the stability and activity of flexible molecules and macromolecules is a theoretical challenge that is gradually gaining more attention. The continuous improvements in computational algorithms and in hardware technologies are greatly expanding the sampling capability of molecular simulations, thereby making a direct positive impact on the feasibility and reliability of entropy predictions. However, more sophisticated theoretical approaches are also required in order to make substantial progress in the type and accuracy of entropy calculations. Focusing on the evaluation of the configurational entropy of single molecules, we highlight recent advances in different methodologies including Gaussian parametric approaches, nonparametric methods and normal mode calculations. For the nonparametric methodologies, we analyze more specifically the importance of correlation effects, the various formulations of the expansion approache