The debate over whether cannabis should be handled as a vilified substance or potential therapeutic entity has persisted over the past 50 years, coupled with or supported by a changing state-level regulatory landscape in the United States. Pharmacists must be aware of potential health implications and keep abreast of regulatory implications likely to result from potential state and national regulation changes. In this commentary, we highlight key considerations for pharmacists in the evolving cannabis regulatory landscape, including historical perspectives, current regulations, and future implications. Special attention to vulnerable populations is outlined, given the potential health consequences that must be considered if cannabis is rescheduled. The substantive public health implications associated with adult cannabis use (e.g., substance use/misuse, driving, lung health) are outside the scope of this commentary.