When establishing threshold values for "driving under the influence of centrally acting compounds" it must be considered that many parameters have an important influence on the pharmacokinetic properties (e.g. volume of distribution, the elimination half-life, and the drug concentration in body fluids) and the pharmacodynamic action (e.g. impairment of skills related to driving). This article describes these inter-and intraindividual parameters from the pharmacokinetic (influence of body weight, age, gender, genetics, diseases, other compounds as ethanol and antacids, enzyme induction, enzyme inhibition, first-pass effects, pharmacokinetic interaction, chronopharmacokinetics, mode of application) and pharmacodynamic (tolerance, pharmacodynamic interaction, pharmacogenetic, chronopharmacodynamic, pathological alterations) point of view. The large variabilities clearly indicate, that preliminary threshold values should be chosen high enough to prevent prejudice of traffic participants. A "consensus value" could be established and continuously monitored by a commission. Beside this the high relevance of valid analytical investigations must be regarded.