This paper will describe some but not all of the highlights in the pharmacology and toxicology of psychotropic substances and explain why future discussions on the use of drugs other than alcohol by drivers will be influenced by recent advances as they can presently be judged. The approach to fifty years of research will be based primarily on discussing the link between human brain and traffic safety and to describe the exciting world of psychopharmacology. This will help us to understand how the human brain under the influence of psychotropic substances is able to affect our behaviour and skills, especially those relating to driving, and thereby affect traffic safety. It is important to realise that recent advances in psychopharmacology will eventually guide us to new classes of drugs, which will be therapeutically superior to old psychotropic medicines because of their lack of unwanted side- effects such as dependence, amnesia and sedation. In reviewing the proceedings of ICADTS conferences over the last decades one can observe the trends in research that support the development of safer drugs for drivers. The exercise clearly shows that ICADTS conferences focussed a great deal on administrative aspects, law enforcement, legal issues relating to drugs other than alcohol and traffic safety. Recently the emphasis in this area has been focussed on changing traffic laws in various European countries to allow law enforcement officers to concentrate more on illicit drug use by drivers. This major step forward in combating drugs and driving has been facilitated by advances in the field of (analytical) toxicology, where the development of on-site devices for screening saliva and urine samples has resulted in the introduction of effective, affordable and easy to use non-instrumental devices. This development will eventually lead to more awareness and understanding of the prevalence of illicit drugs in road traffic. The conclusion is that fifty years of research efforts in the field of drugs and driving has made major contributions to improving traffic safety, although studies to support this view are still lacking.