For about 50 years, clinical pharmacology and therapeutics have been taught in the medical schools via traditional lectures and practical classes. During this time, significant changes have occurred in our understanding of medicine and basic sciences. Also the needs for our community have changed dramatically. The explosion of scientific discoveries, the use of new technologies in disease diagnosis, the availability of a wide range of therapeutic options, and the availability of knowledge to everyone via the Internet have necessitated new approaches for teaching medical and other health professional students. Finding information related to a topic has not become a priority in teaching, what has become more important is to teach undergraduate students how to think in addition to what to think. Applying information learnt and assessing its significance in real life situations has become mandatory. The aims of this paper were: (i) to discuss the model we used in introducing clinical pharmacology and therapeutics teaching in the undergraduate course at the University of Melbourne and the educational principles behind the model, and (ii) to discuss the new tools of assessment used in a problem-based learning (PBL) curriculum.