The U.S. military is keenly interested in curtailing substance misuse among those in its ranks. However, prescription drug misuse (PDM) poses a new type of threat that might be increasing in this population. PDM, particularly of opioid analgesics, can occur among active-duty service members either because of medically indicated use from injuries for which the drug is subsequently overused or because of misuse of others medication. The U.S. Department of Defense is seeking information on how prescription drug use and misuse among service members affects the military and what promising practices can be applied to the military context to prevent and manage (i.e., treat) PDM among military personnel. The Deputy Assistant Secretary of Defense for Readiness asked the RAND Corporation to assist it with these efforts by conducting three tasks: an extensive literature review of the current standards for preventing, identifying, and treating PDM within the military and civilian health systems; assessing, through in-person interviews with frontline medical providers, how widely those practices have been adopted in military medical facilities; and developing a tool that the military could use for projecting current and future rates of PDM among active-duty personnel. This report summarizes the findings from the literature review, documents the process and findings from qualitative interviews on this topic among military health staff, presents the framework for the tool to predict future trends in PDM, and provides key insights based on all of these tasks.