Acamprosate, calcium acetyl homotaurinate, was first developed and tested in the early 1980s in France and has been available in the USA since 2004. Its major mechanism of action is the reduction of cerebral hyperexcitability by interacting with glutamate receptors. More than 20 randomized, placebo-controlled trials have been conducted. With very few exceptions, these studies have demonstrated a significant benefit of acamprosate over placebo. Side effects of acamprosate, such as diarrhoea, are benign and transient. Studies in which acamprosate was given in combination with disulfiram or naltrexone also showed promising results. Further studies are underway to identify potential acamprosate responders on a neurobiological basis. If successful, this would allow an individually targeted prescription of acamprosate that would then further improve its efficacy and cost–effectiveness.