The adverse effects of minor tranquilizers, and more specifically benzodiazepines, on psychomotor and cognitive performance have been documented repeatedly over the years, and epidemiological studies have provided sufficient evidence of their role in traffic accidents. These studies indicate that drug plasma level (DPL) is insufficiently correlated with impairment and that other factors need to be considered in determining the impairment vulnerability. This report reviews several sources of individual variability, particularly as they relate to differential impairment effects. These sources, which include such factors as acute peak effects, acute tolerance, chronic tolerance, benzodiazepine receptor affinity and individual sensitivity, need to be examined before quantification of DPL is introduced as a criterion for driving under the influence. Behavioral testing itself may become the critical means of assessing drug- and/or drug with alcohol-induced driving impairment if acceptable standardized procedures can be developed. Attention is drawn to the rapid onset of impairment associated with acute effects of more lipid soluble drugs. The discussion of impairment of benzodiazepines should be seen in the perspective of their relative overall safety compared to other drugs used as minor tranquilizers.