Sedatives are ubiquitous in the treatment of a variety of different conditions, with benzodiazepines being the chemical class most widely employed. Oversedation with negative effects on cognition, behavior, and functional status are the consequences of toxicity. Although a direct antidote is available, it is rarely used due to fears of withdrawal and seizures. Flumazenil is a benzodiazepine receptor antagonist approved for treatment of sedation and/or coma secondary to effects of GABA-ergic substances. It has been proposed as part of a “coma cocktail” to be given in cases of unresponsiveness of unknown etiology, and has also been effective in reversing paradoxical reactions to benzodiazepines, but flumazenil remains underutilized in clinical practice. At one toxicology center, however, flumazenil is routinely employed in the emergency department and acute hospital setting. It is given as an IV dose of 0.5 mg over 30 seconds, with repeat doses q1-2h PRN to sedated patients with relaxed autonomic indices and peripheral neurologic status. The following reports a six-year retrospective review of the practice and a oneyear close observational study of bedside use of the antidote. 731 patients were treated with flumazenil in the two methods of this study. The overall positive response rate was over 80%. There were no instances of arrhythmias or seizures. No major adverse events were documented for the retrospective study period. In the prospective year, there were 12 instances of side effects to the antidote out of 212 patients treated. No seizures, arrhythmias, or episodes of emesis were observed. Three patients experienced drooling, 7 experienced transient anxiety, and there were 2 separate episodes of odd behavior upon awakening from coma in a patient with CNS disease and personality disorder. Comorbid anxiety disorders were associated with anxiety upon arousal after flumazenil treatment, but no patient required medical intervention for this effect. Chronic use of benzodiazepines and underlying seizure disorders were not contraindications to flumazenil therapy. The antidote was employed in cases of accidental, purposeful, and iatrogenic toxicity to good effect without precipitation of problematic withdrawal. We conclude that flumazenil is a safe diagnostic and therapeutic antidote for cases of suspected toxic sedation. The antidote may prevent airway obstruction and aspiration and facilitate patients’ communication with medical providers. Iatrogenic interventions such as intubation and catheterization may be avoided. Concerns about its use in patients with seizure disorders and/or chronic use of benzodiazepines are unfounded based on our data. Side effects are rare and mild, and can be managed with caregiver presence and behavioral interventions.