The effectiveness of antagonist maintenance with oral naltrexone for opioid dependence has been limited by high dropout rates. Behavioral Naltrexone Therapy (BNT) was developed to improve retention on oral naltrexone by integrating voucher incentives, Motivational and Cognitive Behavioral therapies, and a significant other for monitoring medication adherence. In a 6-month, randomized, controlled trial in heroin dependent patients, BNT (N = 36) improved retention in treatment compared to a standard treatment control (Compliance Enhancement (CE); N = 33) (log rank = 4.28; p = .04). Most patients retained beyond 3 months achieved abstinence from opioids, but retention at 6 months was only 22% on BNT and 9% on CE. A systematic review of related controlled trials revealed similar effect sizes in the small to medium range, and substantial dropout. There may be a limit on the extent to which behavioral therapy can overcome poor adherence to oral naltrexone. Future research should consider combinations of behavioral methods with new long-acting injectable or implantable naltrexone formulations.