Consumption of psychotropic substances (alcohol, drugs, medication) has a major impact on complex activity performance such as driving. This issue is of relevant social interest for the high number of potentially involved subjects and the often fatale outcomes, and affects also occupational physicians because of the high number of people whose job is driving. There are still few studies trying to assess the presence of a possible association between increased risk of accident/injury at work and consumption of psychotropic substances and results are not always in agreement. In spite of such uncertainties and some Italian regulations still worth being amended by Legislator, the possible impact of consumption of psychoactive substances on driving is an issue to be still better defined for which occupational physicians may play a basic role in the field of prevention, clinics and rehabilitation.