Disulfiram treatment, despite its limitations, remains a viable option as a treatment for alcohol dependence and has shown recent promise in treating (1) those with co-morbid alcohol dependence and post-traumatic stress disorder, (2) those with co-morbid cocaine- and alcohol-dependence, and (3) those with cocaine-dependence alone. Although disulfirams mechanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies have uncovered potential anti-craving effects as well as direct effects of disulfiram on cocaine abuse, highlighting a few of the many potential and unique benefits disulfiram may have through its inhibition of dopamine β-hydroxylase. This article will review the major clinical trials of disulfiram spanning nearly 60 years. We will discuss the pharmacodynamics and pharmacokinetics of disulfiram, indications and limitations of its use, suggestions for appropriate patient populations, and monitoring for compliance and adverse effects. We will also review recent literature on newer potential applications for disulfiram use via its unique action on dopamine β-hydroxylase.