Benzodiazepines (BZDs) and related drugs are widely used for treating a variety of conditions (with varying degrees of evidence-base), but their long-term use (more than 2–4 weeks) can be problematic. They were originally thought (or claimed) to be nonproblematic substitutes for barbiturates, but it is now clear that they have their own set of problems. In addition, they are commonly, albeit ill-advisedly, co-prescribed or used nonmedically in combination with other drug substances. The result of such combinations, particularly with the opioids, can be lethal. Administrative and statutory actions notwithstanding, it appears that reducing problems with BZDs will depend on a comprehensive approach that includes improved education for patients, prescribers, regulators, insurers, and the public. First and foremost, however, there is a pressing need for the government to improve its drug-abuse data collection, specifically how it monitors drug-related morbidity and mortality. This chapter reviews the information that demonstrates how an understanding of all of the dynamics is essential for designing effective public-health strategies to reduce BZD-associated problems.