Rational pharmacotherapy is the optimal use of drugs.In a broader sense it encompasses the invention, production, distribution, prescription and technical use of drugs, including ethical and economical aspects.The choice of the right drug is dependent on comparative evaluations of the ratios between therapeutic efficacy and adverse reaction and price, respectively -by knowledge obtained from well-conducted randomised trials.In this process, the principal points are: I) Extrapolations from studies to practice; 2) Differences between statistical significance and clinical relevance; 3) Evaluations of the best parameter of efficacy; 4) Procurement of well designed and relevant studies; 5) Dissemination of knowledge and implementation of strategies to change prescription habits; 6) Counteracting commercial activities from the drug industry; 7) Establishment of indicators of excellent pharmacotherapy; 8) Infringement of the decision ability of the individual doctors; 9) Understanding of economics and balancing the need of the patients with the economic ability of the society; I 0) Quality control of all interventions.It is of paramount importance that clinical pharmacologists is be well trained in these problems enabling them to advice their fellow doctors about the best selection of drugs.This demands a combination of scientific, clinical a nd charismatic skills.Conclusion: Rational pharmacotherapy is to choose the best drug in all clinical situations and knowing bow to implement this choice.It is an integration of scientific knowledge, clinical tradition, ethics, law, economics and persuading abilities.It should be a prime area for clinical pharmacologists showing to society the value of a diversified education.