Because of its exquisite sensitivity to serotonin, the rat stomach fundus was used as a bioassay for serotonin before the development of more quantitative analytical assays for this biogenic amine (Vane 1957). Although the potency for the contractile effects of serotonin has been known for long time, the receptors mediating such a response have eluded definitive characterization for long time. Pharmacological studies attempting to characterize the contractile serotonergic receptor in the rat stomach fundus documented the similarity to the 5-HT2C receptor. In the absence of detectable 5-HT2C receptor mRNA in the rat stomach fundus, only molecular cloning allowed the identification of a new receptor in 1992 in rat and mouse (Foguet et al. 1992; Kursar et al. 1992; Loric et al. 1992; Wainscott et al. 1993) and in 1994 in humans (Choi et al. 1994; Kursar et al. 1994; Schmuck et al. 1994; Wainscott et al. 1996), now called 5-HT2B receptor. Subsequent pharmacological characterization of this receptor subtype in various species identified differences in its pharmacology and confirmed the close identity of this pharmacology to that of 5-HT2C receptors. Its physiological and pathophysiological functions include many differentiation steps both in periphery and central nervous system that were not previously identified or attributed to other receptor subtypes.