Alcohol misuse, or unhealthful alcohol use, which includes the full spectrum from drinking above recommended limits (i.e., risky/hazardous drinking) to alcohol dependence, is associated with numerous health and social problems, more than 85,000 deaths per year in the U.S., and an estimated annual cost to society of more than $220 billion. Alcohol misuse is estimated to be the third leading cause of preventable mortality in the U.S., following tobacco use and being overweight. In the past, alcohol-use disorders (AUDs) included harmful use, alcohol abuse, and alcohol dependence. Diagnostic criteria for AUDs have evolved. Prevalence of AUDs is higher for men than for women, with estimates indicating a lifetime risk of more than 20 percent for men. Alcohol dependence has lifetime prevalence rates of about 17 percent for men and 8 percent for women. AUDs cause substantial morbidity and mortality-threefold to fourfold increased rates of early mortality. They are associated with hypertension, heart disease, stroke, cancer, liver cirrhosis, amnesias, cognitive impairment, sleep problems, peripheral neuropathy, gastritis and gastric ulcers, pancreatitis, decreased bone density, anemia, depression, insomnia, anxiety, suicide, and fetal alcohol syndrome. Excessive alcohol consumption is also a major factor in injury and violence. Acute alcohol-related harm can be the result of fires, drowning, falls, homicide, suicide, motor vehicle crashes, child maltreatment, and pedestrian injuries. In addition, AUDs can complicate the assessment and treatment of other medical and psychiatric problems. The use of medications for AUDs is associated with uncertainty and variation across providers and settings. Since the last report, there has been more than a tenfold increase in the number of individuals studied in controlled clinical trials of naltrexone and acamprosate, and many trials of medications that are not FDA approved. Other reasons for conducting a new review on this topic include the following: (1) to assess the comparative effectiveness of the FDA-approved medications; (2) to determine whether any agents that are not FDA approved have evidence supporting their efficacy; (3) to evaluate the evidence on intramuscular naltrexone, a fairly recently approved medication; (4) to evaluate whether trials provide evidence of effectiveness in primary care settings; (5) to assess whether some medications are more or less effective for adults with specific genotypes; and (6) to provide a comprehensive review of medications for AUDs that is relevant for clinicians, researchers, and policymakers. This report focuses on clinically relevant medications-those commonly used, those with sufficient literature for systematic review, and those of greatest interest to clinicians and to the developers of guidelines. The following Key Questions addressed include: KQ 1a: Which medications are efficacious for improving consumption outcomes for adults with AUDs in outpatient settings? KQ 1b: How do medications for adults with AUDs compare for improving consumption outcomes in outpatient settings? KQ 2a: Which medications are efficacious for improving health outcomes for adults with AUDs in outpatient settings? KQ 2b: How do medications for adults with AUDs compare for improving health outcomes in outpatient settings? KQ3a: What adverse effects are associated with medications for adults with AUDs in outpatient settings? KQ 3b: How do medications for adults with AUDs compare for adverse effects in outpatient settings? KQ 4: Are medications for treating adults with AUDs effective in primary care settings? KQ 5: Are any of the medications more or less effective than other medications for men or women, older adults, young adults, racial or ethnic minorities, smokers, or those with co-occurring disorders? KQ 6: Are any of the medications more or less effective for adults with specific genotypes (e.g., related to polymorphisms of the mu-opioid receptor gene [OPRM1])?