Designer benzodiazepine (DBZD) use has been increasing over the past decade and poses a threat to human health and safety, particularly when involved in driving under the influence of drugs (DUID) cases. Over a five-year period between 2017 and 2021, there were 1145 reported DBZDs in 805 blood samples submitted from law enforcement agencies for DUID testing. Eleven different DBZD were detected, including three metabolite pairs: etizolam/alpha-hydroxyetizolam, clonazolam/8-aminoclonazolam, diclazepam/delorazepam, flualprazolam, flubromazolam, flubromazepam, bromazolam, and bromazepam. Etizolam/alpha hydroxyetizolam (n=485) and flualprazolam (n=149) were the most frequently detected DBZD, at 60% and 18%, respectively. Driving behavior, standardized field sobriety tests (SFST) performance, and physical observations of individuals suspected of DUID, whose blood was toxicologically confirmed for one or more DBZD, were consistent with effects caused by central nervous system (CNS) depressants. Each DBZD has its own unique timeline, and toxicology testing had to be frequently updated to reflect the state of the novel psychoactive substance (NPS) market. DBZD play a role in impaired driving and can be the sole intoxicant in DUID cases.