A developing trend in exploring the sites at which drugs act is to use molecular rather than chemical agents to alter receptors, intracellular signalling mechanisms or gene expression. The 5-HT neurotransmission system is targeted by drugs useful in many behavioural disorders, including anxiety, depression, psychosis and eating disorders. It also regulates many physiological functions and provides some examples of the potential use of these new molecular approaches. This article reviews the progress made in the molecular manipulation of 5-HT receptors and discusses the potential of such tools for the treatment of diseases associated with the 5-HT transmission system.