The legacy of the past, the reality of the present and the hopes of the future

We have never been so close to realising the dream of the pharmaceutical industry: that we may be able to design new drugs from first principles. However, there are still enough unknown areas where computational medicinal chemists can successfully use their sagacity and creativity. A personal point of view on the present approaches aimed for a rational drug design is given here. Perspectives on future developments in this field are also outlined in this assessment.