There is a poor insight in the fundamental relations between the physico-chemical characteristics and the biological properties of the potential drug candidates. This includes mechanisms of molecular interaction and signal transduction, processes of drug disposition (absorption, distribution, metabolism, excretion) and the aspect of drug safety and toxicity on a long-term basis. In silico modeling using computer power and rule-based and expert knowledge has begun to prove its importance in both prediction of molecular interaction and 'directed evolution' of drug candidates. Also other areas of the drug development process can be modeled in silico. Exciting new areas with respect to the latter are cell function and disease modeling, simulation of clinical trials, and its application in (pre)-clinical PK/PD modeling.