Until recently, much of our knowledge of the neuropharmacology of addiction was derived from animal studies, but we are now able to study the human brain directly and there is a growing body of knowledge on the underlying neuropharmacology of addiction. Addiction is increasingly viewed as a disorder of motivated behaviour and the following brain structures are thought to be crucial in the circuitry of reward and motivation: the orbitofrontal cortex (for stimulus evaluation); the nucleus accumbens (predicting rewards); and the amygdala (response to primary stimuli). Nearly all substances of abuse cause an increase in synaptic dopamine, although through different mechanisms, and dopamine is implicated in the development of addiction, with an important role particularly in the pairing of drug-related cues with responses. In end-stage addiction, however, changes in the synaptic strengths of glutamate fibres from prefrontal cortex to nucleus accumbens have a major effect. These changes may underlie the switch from impulsive substance use to compulsive substance use that seems to occur in addiction. A reduction in post-synaptic dopamine D 2 receptor levels following alcohol or stimulant dependence may be involved in the sensation of craving. In general, dysfunction of the neural circuitry of reward and motivated behaviour may be the neural substrate for the development and maintenance of addiction. The neuropharmacology of specific substances such as alcohol, stimulants, opioids, cannabis, ecstasy (MDMA) and nicotine are varied, but different substances disrupt different parts of this circuitry to give the same net effect – namely addiction.