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Acamprosate (calcium acetylhomotaurine) is an amino acid modulator that has displayed efficacy in some clinical trials in reducing craving and promoting abstinence in alcohol dependent patients following detoxification. While acamprosate is safe and generally well-tolerated, not all studies have demonstrated clinical efficacy that is superior to placebo. In addition, the precise neurochemical mechanisms of action of acamprosate have still not yet been identified. In this review, we summarize current clinical data on the safety, efficacy, and pharmacokinetic properties of acamprosate, as well theories on its potential mechanism of action. We also discuss tolerability and patient preference issues and conclude with a discussion of the place of acamprosate in addiction medicine and therapy.