Aqueous drug solubility and intestinal drug permeability are two of the most important factors influencing drug absorption. If the developability of a drug is to be included in the lead optimization, new experimental and computational models of solubility and permeability are needed. These models must have the capacity to handle a large amount of data. Nowadays, epithelial cell culture models such as Caco-2 are routinely used to assess intestinal drug permeability and transport in drug discovery settings. The permeability values obtained from the Caco-2 cell monolayers have been traditionally used to devise in silico models for the prediction of drug absorption. In this paper, the use of molecular surface areas as descriptors of permeability and solubility will be reviewed. Moreover, a virtual filter for the prediction of oral drug developability based on the successful combination of in vitro and in silico models of drug permeability and aqueous drug solubility will be discussed.