Nonmedical use of prescription medications--particularly controlled substances--has risen dramatically in recent decades, resulting in alarming increases in overdose-related health care utilization, costs, and mortality. The Centers for Disease Control and Prevention estimate that 80% of abused and misused controlled substances originate as legal prescriptions. As such, policymakers and payers have the opportunity to combat nonmedical use by regulating controlled substance accessibility within legal prescribing and dispensing processes. One common policy strategy is found in Medicaid controlled substance lock-in programs. Lock-in programs identify Medicaid beneficiaries exhibiting high-risk controlled substance seeking behavior and "lock in" these patients to, typically, a single prescriber and pharmacy from which they may obtain Medicaid-covered controlled substance prescriptions. Lock-in restrictions are intended to improve care coordination between providers, reduce nonmedical use behaviors, and limit Medicaid costs stemming from nonmedical use and diversion. Peer-reviewed and gray literature have been examined to assess the current prevalence and design of Medicaid lock-in programs, as well as the current evidence base for informing appropriate program design and understanding program effectiveness. Forty-six state Medicaid agencies currently operate lock-in programs. Program design varies widely between states in terms of defining high-risk controlled substance use, the scope of actual lock-in restrictions, and length of program enrollment. Additionally, there is a remarkable dearth of peer-reviewed literature evaluating the design and effectiveness of Medicaid lock-in programs. Nearly all outcomes evidence stemmed from publicly accessible internal Medicaid program evaluations, which largely investigated cost savings to the state. Lock-in programs are highly prevalent and poised to play a meaningful role in curbing the prescription drug abuse epidemic. However, achieving these ends requires a concerted effort from the academic and policy communities to rigorously evaluate the effect of lock-in programs on patient outcomes, determine optimal program design, and explore opportunities to enhance lock-in program impact through coordination with parallel controlled substance policy efforts, namely prescription drug-monitoring programs.