Most of the cloned serotonin (5-HT) receptor subtypes are present on enteric neurons that control gastrointestinal function. Because of the wide distribution of 5-HT receptor subtypes in the gut, the precise actions of currently marketed drugs are unclear. Furthermore, efficacy of these drugs varies between individuals. Two recent advances provide important potential explanations for this phenomenon: polymorphisms have recently been discovered in the gene for the key enzyme in neural 5-HT production, and physiologically relevant 5-HT(4) receptor splice variants have been shown to be differentially located across intestinal regions. Functional 5-HT(7) receptors have recently been demonstrated in the gut and, together with the 5-HT(1A) receptor, offer new therapeutic options. In addition, recently suggested identities for the elusive 5-HT(1P) receptor could result in other, more effective therapeutic targets.