Mortality statistics for excessive alcohol consumption show no signs of abatement, with a report published in 2011 from the World Health Organization (WHO) estimating that 2.5 million people worldwide died because of their alcohol consumption. Serious physiological, psychological, social and legal problems are thought to affect many more. Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition that often occurs in those individuals who significantly reduce or stop their intake after a prolonged and excessive period of drinking. Pharmacological treatment of the AWS has traditionally been undertaken by the use of the benzodiazepines, but recent years have witnessed the emergence of several alternatives. The aim of this paper was (1) to review the evidence base supporting the use of various pharmacological agents currently employed to treat AWS, and (2) to consider the efficacy and safety of the emerging alternatives to the benzodiazepines. The Cochrane Database of Systematic Reviews, CINAHL, Embase, PsycINFO, MEDLINE and BNI databases were extensively searched in order to retrieve the maximum number of relevant articles. Reference lists from relevant literature were also used to identify other potential studies for inclusion. All studies concerned with measuring the efficacy and safety of the various pharmacological treatment options for AWS were considered and a total of 63 trials were included in this review. Findings support the use of benzodiazepines as the recommended drug of choice for the treatment of AWS in the absence of adequate evidence to support the use of alternative agents. There is a lack of evidence of a superior pharmacological agent to the benzodiazepines for the treatment of AWS. There are several studies that have shown that there are pharmacological alternatives that could compete or act as an adjunct with the benzodiazepines in terms of high efficacy and safety in the treatment of AWS, but there is a need for further quality research to be carried out before definitive conclusions can be drawn.