Recently, one of the key trends in the pharmaceutical industry has been the integration of what have traditionally been considered 'development' activities into the early phases of drug discovery. The aim of this paradigm shift is the prompt identification and elimination of candidate molecules that are unlikely to survive later stages of discovery and development. In this review, the authors examine the growing role that is being played by computational methods in this filtering process, with a particular focus on the prediction of intestinal absorption and blood-brain barrier penetration.