Since chlordiazepoxide was introduced in 1961, the benzodiazepines have had many important roles in the pharmacotherapy of various disorders. This drug class for the central nervous system has been considered one of the safest in use for 35 years, especially when the benzodiazepines are compared with the barbiturates they often replaced. The objective of this article is to provide an update on the availability and distribution of benzodiazepines around the world and to discuss their most common clinical applications. Adverse effects of benzodiazepines, observed after long-term therapeutic use and after overdoses, are also presented. Triazolam is discussed because this benzodiazepine was removed from the market by regulatory authorities in the United Kingdom in 1991. Benzodiazepines will continue to have an important role in clinical medicine. Their clinical use, however, should be monitored more closely because of the greater awareness of their adverse effects after long-term use and because of the potential for misuse and abuse.