Translational medicine is the drug development phase in which preclinical and clinical applied research is conducted to aid dose and disease selection with great financial impact. Thus, during this phase, early discontinuation of a drug that will later fail due to drug interactions is a must for a proper resource allocation. It is not only important to identify a potential interaction, but also to be able to differentiate between detectable interactions and clinically relevant interactions. Due to the scientific advancement, the prediction of drug interactions during translational medicine has shifted from empirical/observational to rational based. These investigations are thus in line with the FDA's Critical Path Initiative and are facilitated by the availability of mature technologies and by current European and US guidelines for both in vitro and in vivo studies. Because drug interactions must be evaluated in a multidisciplinary fashion, even if these studies are contracted externally, pharmaceutical companies should be directly involved in the conduction of such studies to fully exploit their potential and to allow a better and faster interpretation of the results.