The conformational energy of a molecule in solution consists of two components: the intramolecular potential energy of the molecule and the solvation free energy of the molecule, the latter describing its interaction with the solvent. Although the intramolecular potential energy of small organic molecules can be calculated to a high degree of accuracy with modern Quantum Mechanical methods, biological macromolecules such as proteins and nucleic acids are far too large for the application of these methods. Alternative strategies for estimating the intramolecular potential energy have had to be devised for these molecules. These can be broadly classifed as physical effective energy function (PEEF) methods and statistical effective energy function (SEEF) methods. PEEFs attempt to reproduce the true Born-Oppenheimer surface of the molecule. This class contains the various Molecular Mechanics force fields. SEEFs are derived from the statistical analysis of the known 3D structures of biological macromolecules and attempt to reproduce the observed frequencies of given features in these structures. This class contains, among many others, the protein threading potentials. As for solvation, the most direct strategy consisting of modelling solvent molecules explicitly is usually too slow for most applications. Therefore, several implicit solvent solvation models have been developed to estimate the solvation free energy of a molecule. In this talk, I describe the general features of PEEF and SEEF methods, as well as the directions current research on the development of these methods is taking. I will also give an overview of the solvation methods most commonly applied to biological macromolecules. These will include, among others, the Poisson-Boltzmann method and the Langevin Dipoles method.