This article introduces a special isssue of Current Pharmaceutial Design focusing on the various side effects of benzodiazepine medications. We argue that an increased awareness of the risk of dependence, withdrawal symptoms upon discontinuation, and cognitive side effects of the benzodiazepines has likely contributed to the decline in their prescription rate over the last two decades, as has increased availability of alternative pharmacologic and non-pharmacologic treatments for anxiety and insomnia. The present special issue consists of series of five papers covering current issues in the area of benzodiazepine side effects. These reviews cover a wide range of topics pertaining to adverse, unintended consequences of this class of pharmacologic agents including their potential for tolerance and withdrawal, their profile of associated cognitive impairments, as well as current understanding of means for minimizing these unintended effects. The reviews also cover a variety of methodologies and disciplines from laboratory-based research findings with animals, to laboratory-based studies wth healthy human volunteers, to findings obtained in the clinic with anxious pat ients. All reviews are timely contributions, covering highly relevant topics for consideration of benzodiazepine side effects at present. The papers presented herein should serve to stimulate future research that may ultimately help improve the quality of life of those patients living with debilitating anxiety-related conditions.