For patients afflicted with symptoms of anxiety and insomnia, benzodiazepines are generally a safe and effective short-term pharmacological treatment option. Although considered safer than other sedative-hypnotic medications, substantial concern exists regarding the addictive nature and abuse potential of benzodiazepines along with potentially inappropriate prescribing and utilization in clinically vulnerable populations. These medication misadventures can have a significant impact on public health. Examples of medication misadventures as they pertain to benzodiazepines include the prescribing and use in clinically vulnerable populations for whom they are contraindicated or their efficacy has not been evaluated, the development of tolerance or addiction, abuse of the medication, and the manifestation of negative health outcomes including cognitive impairment, withdrawal symptoms upon discontinuation, or the reoccurrence of a preexisting substance use disorder. In order to better understand medication misadventures associated with benzodiazepines retrospective analyses using populations extracted from large health claims databases are employed. To understand how benzodiazepine use may lead to adverse events causing patient harm, the risk of exacerbations in benzodiazepine users diagnosed with chronic obstructive pulmonary disease was estimated. The inherent risk of benzodiazepine addiction and abuse was estimated in an HIV-infected population, a population with a high prevalence of substance use disorders. This risk was estimated by first determining whether HIV-infected individuals are more likely to have any benzodiazepine use compared to their uninfected counterparts, and secondly, by examining the association between HIV-infection and potentially problematic benzodiazepine use. Finally, in an effort to mitigate unexpected and undesirable consequences to public health associated with the prescription drug abuse epidemic in the US, states have implemented prescription drug monitoring programs (PDMPs) to track the prescribing and dispensing of controlled substance medications. The effect of these programs on benzodiazepine dispensing is evaluated on a state and national level. Findings will provide healthcare professionals a better understanding regarding the risk of medication misadventures involving benzodiazepines when evaluating their appropriateness in patients with anxiety, depression, and insomnia. Additionally, policymakers will understand the implications of PDMPs on the dispensing of benzodiazepines as they become a more widely used tool to combat prescription drug abuse and diversion.