Much progress has been made in GABAB receptor pharmacology since the discovery of this receptor in 1980. Selective agonists and antagonists have been developed and a functional role for the receptor as a mediator of slow inhibitory postsynaptic potentials in many brain regions has emerged. In this article, Norman Bowery discusses the evidence for heterogeneity of GABAB receptors, their possible physiological and pathological roles and the therapeutic potential of GABAB receptor agonists and antagonists.