There is a discrepancy between the recommendation for caution and daily practice in the prescription of benzodiazepines. Although there is heterogeneity in the registered indications, all benzodiazepine agonists have almost the same mechanism of action. There are, however, substantial pharmacokinetic differences between individual benzodiazepine agonists. During short-term use of benzodiazepines, the elimination half-life is no measure of duration of action. Benzodiazepine lipophilicity determines the speed of action. If a rapid effect is desired, for instance in acute anxiety or agitation, then regarding oral medication the use of a lipophilic benzodiazepine such as diazepam is a rational choice. An accumulation factor can be used to estimate benzodiazepine accumulation during chronic use. In theory, accumulation does not occur with once-daily dosage of benzodiazepines that have an elimination half-life markedly shorter than 24 h, such as oxazepam, temazepam, and lorazepam.