Long-term relapse prevention is the biggest challenge in treating alcohol-dependent patients. It is equally based on psychotherapy and pharmacotherapy. Psychotherapy includes motivational interviewing, community reinforcement, cognitive behavioural therapy, motivational enhancement, twelve-step facilitation, social network behaviour therapy, cue exposure, etc. For pharmacological treatment, we dispose of disulfiram, acamprosate and naltrexone. Reviews and meta-analyses reveal only modest effect sizes of these approaches probably because they are usually tested in large and heterogeneous samples where "one size does not fit all". However, attempts to form more homogeneous subgroups for which specific psychotherapies should be more effective ("matching") also failed. We suppose that this failure may have to do with the fact that these studies used only psychopathology and behavioural analyses as a basis for subtyping. Things look more promising once biologically defined endophenotypes are used as well in order to form more homogeneous subgroups. For example, naltrexone treatment seems more effective in carriers of a specific variant of the mu-opioid receptor gene. The same could be true for acamprosate if a newly found polymorphism was used to preselect potential responders. Very recently biological differences between patient groups are also being detected using functional imaging. Naltrexone is suggested to work better in a subgroup of patients with higher cue reactivity when shown appetitive alcohol pictures. MR spectroscopy of brain glutamate levels may detect potential acamprosate responders. On such a basis, an individualised approach in the treatment of alcoholism ("personalised medicine") seems to hold promise.