The development of molecular, and statistical thermodynamic modeling tools for estimation and correlation of solubility of crystalline solutes in solvents is a subject of enormous importance in the pharmaceutical industry. Optimization of extraction, chromatography, and crystallization processes require screening of numerous solvent systems for which the solubility of the compound of interest has to be measured as a function of temperature. The use of molecular thermodynamic models for estimating solubility of solid solutes in solvents, using minimum experimental data, have been reported in the literature. For general application of these models, thermodynamically consistent ideal solubility data is required. A reasonable estimate of the difference in the molar heat capacity of the solid and the hypothetical super-cooled liquid form of the solute, and since parameter is usually not known, three assumptions have been commonly used in the literature, and these are, the parameter: i) has negligible dependence on temperature and hence can be determined by extrapolation to the melting temperature, ii) can be considered to be zero, and iii) is an approximate of the molar entropy of fusion. Despite the widespread use of these assumptions for correlating solubility data, a procedure for testing and validating the appropriate choice (to ensure consistency) remains to be established. A material-conserving analytical method (with in-line reversed-phase HPLC) was used to measure the equilibrium solubility of lovastatin, and simvastatin in a family of alcohols, acetates and ketones. Thermodynamic consistency was established when the first assumption was used in the ideal solubility calculation. Employment of molecular simulation to gain insights into the solubility behavior of solid solutes in liquid solvents, and the application of free-energy perturbation (FEP) calculations, and their use for computation of relative free energies of solvation to guide solvent selection, for pharmaceutical application, will be introduced.