Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted. The search term used was ‘(dependence OR withdrawal) AND pregabalin’. No other date limits were set and no language restrictions were applied. Works cited in identified articles were cross-referenced and personal archives of references also searched. Articles were included based on the expert opinions of the authors. There is limited evidence supporting the role of pregabalin for the treatment of physical dependence and accompanying withdrawal symptoms associated with opioids, benzodiazepines, nicotine, cannabinoids, and alcohol, although data from randomized controlled studies are sparse. However, the current evidence is promising and provides a platform for future studies, including appropriate randomized, placebo- and/or comparator-controlled studies, to further explore the efficacy and safety of pregabalin for the treatment of withdrawal symptoms. Given the potential for pregabalin misuse or abuse, particularly in individuals with a previous history of substance abuse, clinicians should exercise caution when using pregabalin in this patient population.