Up to half of individuals with a history of long-term, heavy alcohol consumption will experience the alcohol withdrawal syndrome (AWS) when consumption is significantly decreased or stopped. In its most severe form, AWS can be life-threatening. Medically assisted withdrawal (MAW) often forms the first part of a treatment pathway. This clinical review discusses key elements of the clinical management of MAW, necessary adjustments for pregnancy and older adults, likely outcome of an episode of MAW, factors that might prevent completion of the MAW process and ways of overcoming barriers to ongoing treatment of alcohol use disorder. The review also discusses the use of benzodiazepines in MAW. Although there is clear evidence for their use, benzodiazepines have been associated with abuse liability, blunting of cognition, interactions with depressant drugs, craving, delirium, dementia and disrupted sleep patterns. Because glutamatergic activation and glutamate receptor upregulation contribute to alcohol withdrawal, anti-glutamatergic strategies for MAW and other potential treatment innovations are also considered.