During the discovery stage in lead identification/optimization, compounds are characterized for their solubilities in biorelevant media and these data are often used to model the in vivo behavior of the compounds and predict the fraction absorbed. These media are selected to closely approximate the composition of human intestinal fluid. Owing to the complexity and variability in human intestinal fluid composition, it is essential that the chosen simulated media mimic the in vivo condition as closely as possible. Several recipes have been developed and are routinely used in assessing the solubilities of compounds. It is necessary to revisit these recipes and modify them as the understanding of the human GI tract increases. In the present work, we have evaluated the solubilities of six model compounds in several media and have proposed slight modifications to the currently used recipes based on our own data and that reported in the literature.