Substance dependence is a major health problem but increasing understanding of its neurobiology is likely to lead to improved prevention and treatment. Fundamental aspects of dependence include tolerance and withdrawal and the fact that the drug becomes the centre of the addict's world. Neuroimaging has been key in defining underlying neurobiological mechanisms. The activity in particular brain regions has been shown to be altered in addiction. These include the anterior cingulate which is involved in emotional salience and the orbitofrontal cortex, involved in impulse control. Dopamine is the key neurotransmitter since most abused drugs increase its levels, and many pharmacotherapies have targeted this system. The opiate system is also key in mediating the pleasurable effects of some drugs such as alcohol by increasing dopamine levels. The GABA and glutamate systems mediate many of the other effects of alcohol. As the neurobiology of different components of addiction become evident, pharmacological approaches involve exploiting our new understanding which will likely lead to improved treatments.