Increasing evidence suggests that craving may play a central role in the mechanisms of addiction. The experience of craving is largely characterized by obsessional thoughts about drugs, triggering compulsive drug-seeking and drug-taking behaviour. In the present article the possible involvement of brain 5-hydroxytryptamine (5-HT) in the mechanisms of craving and relapse is discussed by integrating the results of basic research with those obtained in human studies. Based on studies suggesting that the brain serotonergic system plays a central role in the regulation of impulse-control mechanisms, it is proposed that 5-HT deficiency may contribute to the loss of control over drug-taking, which is a crucial factor for the maintenance of addictive behaviour.