Alcohol dependence is one of the leading causes of morbidity worldwide, yet only a minority of those afflicted engages in treatment. While increasing access to treatment is an important public health approach, increasing the success of treatment is also likely to lead to greater engagement. However, alcohol dependence is a complex disorder likely to consist of several biological subtypes. Recent evidence from a number of different studies has suggested that genetic variation in the mu-opioid receptor has a significant influence on clinical presentation of alcohol problems and response to treatment with an opioid antagonist. Most notably, the A118G polymorphism of the mu-receptor gene has been demonstrated to predict clinical response to naltrexone in alcohol-dependent individuals. This article reviews the biological correlates and outlines a scientific agenda for better understanding the role of opioid neurotransmission in the etiology, maintenance and treatment of alcohol dependence.